Nooshafarin Safadel; Parisa Dahim; Siamak Mirab Samiee; Katayoon Khodaverdian; Maryam Mir Mohammad ali Roodaki; Soghra Anjarani; Shahla Farsi; Mahdi Rafiee; Marjan Rahnamaye Farzami
Abstract
Background & Objective: Providing equitable access to good quality, timely, and affordable laboratory testing has always been a top priority for the Ministry of Health and Medical Education (MoH-ME) and the Reference Health Laboratory (RHL). Considering the significant role of medical laboratories ...
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Background & Objective: Providing equitable access to good quality, timely, and affordable laboratory testing has always been a top priority for the Ministry of Health and Medical Education (MoH-ME) and the Reference Health Laboratory (RHL). Considering the significant role of medical laboratories in disease surveillance, RHL developed a strategic plan to manage laboratory services during the COVID-19 pandemic based on the “Strategic Framework for strengthening health laboratory services, 2016-2020” proposed by the World Health Organization (WHO). This article describes the steps taken to establish the strategic framework in Iran.Methods: Firstly, a National Laboratory Committee was formed in MoH-ME and a situation analysis was conducted to explore the strengths, weaknesses, opportunities, and threats in different components of our laboratory system. Gaps and resources needed to address those gaps were determined; then, RHL outlined operational processes and mechanisms for monitoring the activities.Results: The WHO strategic roadmap and its six strategic goals concerning leadership, quality, human resources, safety and security, laboratory networking, and rational use of laboratory testing, helped us to promote national laboratory services in accordance with health system requirements in the COVID-19 pandemic.Conclusion: The establishment of a national molecular laboratory network with more than 500 laboratories from different sectors may result in timely access to countrywide laboratory services and would be beneficial for future COVID-19 and/or other viral outbreaks. Continual evaluation of the COVID-19 laboratories' performance, production of PCR test kits by the local manufacturers, and development of a platform for virtual training would be other accomplishments that Iran achieved in coping with the recent pandemic.
Uropathology
Ali-Ahmad Bayat; Niloufar Sadeghi; Ghazaleh Fazli; Mohammad Reza Nowroozi; Solmaz Ohadian Moghadam; Amin Radmanesh; Mohammadjavad Hedayatshodeh; Ali Reza Sarrafzadeh; Omid Zarei; Fatemeh Ghaemimanesh; Hodjattallah Rabbani
Abstract
Background & Objective: Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as ...
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Background & Objective: Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma.Methods: The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated.Results: A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis.Conclusion: The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.
Hematopathology
Hossein Ayatollahi; Ali Bazi; Mohammad Hadi Sadeghian; Ali Fani; Payam Siyadat; Maryam Sheikhi; Omolbanin Sargazi-aval
Abstract
Background & Objective: Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) is a relatively common subtype of acute myeloid leukemia (AML). Here, our objective was to ascertain the survival of patients with this leukemia in north-east of Iran. Methods: Survival rates of ...
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Background & Objective: Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) is a relatively common subtype of acute myeloid leukemia (AML). Here, our objective was to ascertain the survival of patients with this leukemia in north-east of Iran. Methods: Survival rates of 42 APL patients with t(15;17)(q22;q12) were assessed. Clinical information was obtained from archived medical records. Statistical analysis was performed by SPSS 18 software using log-ranked test and Kaplan Maier survival analysis. Results: Females and males comprised 49% and 51%, respectively. The mean age at diagnosis was 34.3 ± 14.1 years old. During the study period, 17 demises occurred in males, while this number was 7 in females. The mean survival of patients (month) was 23.22 ± 3.57 (95% CI: 16.21 ± 30.2). The five-year survival rate obtained 30%. Regarding demographic and clinical features, the highest rates of 5-year survival were recorded in patients with 20-35 years old (47.6%), males (51%), white blood cell count <10±/l (48%), and platelet count >140 ± /l (100%). Conclusion: Younger age, lower WBC count and higher platelet count were significantly associated with longer survival in AML patients with t(15;17)(q22; q12).
Breast Pathology
Aiat Shaban Hemida; Reham Ahmed Abdelaziz; Moshira Mohammed Abd El-Wahed; Nancy Youssef Asaad; Marwa Mohammed Serag El-Edien; Hend Ali Elshahat
Abstract
Background & Objective: The regulator of chromosome condensation 2 (RCC2) and RAS-related C3 botulinum toxin substrate 1 (Rac1) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p53/RCC2/Rac1 has been proposed to contribute to ...
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Background & Objective: The regulator of chromosome condensation 2 (RCC2) and RAS-related C3 botulinum toxin substrate 1 (Rac1) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p53/RCC2/Rac1 has been proposed to contribute to the regulation of colon cancer metastasis. However, until now, this pathway has not been thoroughly investigated in breast cancer. This study seeks to explore the influence of immunohistochemical expression and the correlation among RCC2, Rac1, and p53 in breast infiltrating ductal carcinoma (IDC).Methods: Immunostaining was performed on 120 breast IDC specimens using RCC2, Rac1, and p53 antibodies. Statistical analyses were conducted to examine the correlations between these antibodies.Results: A Positive expression of RCC2, Rac1, and p53 was observed in 116 (96.7%), 120 (100%), and 33 (27.5%) of the breast cancer cases, respectively. RCC2, Rac1, and p53 demonstrated association with poor prognostic parameters such as frequent mitoses, high Ki-67 status, positive lymphovascular invasion (LVI), and advanced tumor stage. A highly significant direct correlation was found between each immunohistochemical marker and the other two markers. Shorter overall survival was linked to multifocal tumors (P=0.017), advanced tumor stage (T3) (P=0.010), Luminal B subtype (P=0.015), progressive disease (P=0.003), positive Her2neu status (P=0.008), and metastasis to distant organs (P<0.001). However, RCC2, Rac1, and p53 did not exhibit a significant association with overall survival.Conclusion: The high expression levels of RCC2, Rac1, and p53 in breast IDC suggest their potential role in tumor behavior. The association of RCC2 and Rac1 with poor prognostic parameters may serve as predictive indicators for aggressive tumors, thus implying that targeted therapy could be beneficial in the treatment of breast cancer.
Hematopathology
Chethana Babu Udupa; KARTHIK UDUPA; Ananth Pai; Prathika Sherigar
Abstract
Background & Objective: Cytogenetic abnormalities in Multiple myeloma (MM) has emerged as the most important factor that determine the prognosis and survival. Fluorescence in situ hybridization (FISH) can detect a greater number of cytogenetic abnormalities as compared to conventional karyotyping ...
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Background & Objective: Cytogenetic abnormalities in Multiple myeloma (MM) has emerged as the most important factor that determine the prognosis and survival. Fluorescence in situ hybridization (FISH) can detect a greater number of cytogenetic abnormalities as compared to conventional karyotyping and hence has become the standard test in determining genetic abnormalities in MM. The present study was planned as there is an unmet need to find out various cytogenetic abnormalities and to implement them in prognostic stratification by Revised International Staging System (R-ISS) among Indian population. Methods: A single institution retrospective study was conducted among a total of 117 patients newly diagnosed as Multiple Myeloma. They were analyzed for various cytogenetic abnormalities by using interphase FISH (iFISH) and were staged according to Revised International Staging System (R- ISS). Results: Out of the 117 patients studied, deletion 17p13 (p53) was present in 16 patients (13.67%). Thirty patients (25.64%) showed deletion 13q14.3. Three patients (2.56%) were detected to have t(4:14).Two patients (1.7%) had t(11:14) and t(14:16), respectively. Total of 19 patients (16.23%) in our study exhibited high risk cytogenetics and two among them had more than one high risk cytogenetic abnormalities. There was a 66.4% moderate correlation between ISS-III and high-risk cytogenetics which was statistically insignificant. Of the total 117 patients, 37 (31.62%) were staged R-ISS III. Conclusion: High risk cytogenetics was found in 16.23 % of our study population and del 17p13 was the most common high-risk cytogenetic abnormality. Of the studied subjects, 31.62% had R-ISS III, which is significantly higher compared to western population.
Breast Pathology
Mahdi Fatemizadeh; Farzaneh Tafvizi; Farzaneh Shamsi; Sahar Amiri; Afsaneh Farajzadeh; Iman Akbarzadeh
Abstract
Background & Objective: Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications ...
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Background & Objective: Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications are used concurrently. Also, combining the drugs with nanocarrier has become an important strategy in targeted therapy. This study is designed to assess the apoptosis induction, cell cycle arrest, and anti-cancer potential of Tamoxifen-Curcumin-loaded niosomes against MCF-7 Cancer Cells.Methods: A novel niosomal formulation of tamoxifen-curcumin with Span 80 and lipid to drug ratio of 20 was employed. The MCF-7 cells were cultured and then treated with IC50 value of tamoxifen-curcumin-loaded niosomes, the combination of tamoxifen and curcumin, tamoxifen, and curcumin alone. Flow cytometry, Real-Time PCR, and cell cycle analysis tests were conducted to evaluate the induction of apoptosis.Results: Drug-loaded niosomes caused up-regulation of bax and p53 genes and down-regulation of bcl2 gene. Flow cytometry studies showed that niosomes containing tamoxifen-curcumin increased apoptosis rate in MCF-7 cells compared to the combination of tamoxifen and curcumin owing to the synergistic effect between the two drugs along with higher cell uptake by formulation niosomal. These results were also confirmed by cell cycle analysis.Conclusion: Co-delivery of curcumin and tamoxifen using optimized niosomal formulation revealed that at acidic pH of MCF-7 cancer cells, released drugs from niosomal carriers would be more effective than physiological pH. This feature of niosomal nanoparticles can reduce the side effects of drugs in normal cells. Niosomal nanoparticles might be used as a biological anti-cancer factor in treatment of breast cancer.
Oral Pathology
Pooja Sharma; Anjali Narwal; Mala Kamboj
Abstract
Background & Objective: Cell population and turnover are controlled by a balance between cell proliferation and apoptosis. Detection of apoptosis in oral cancer contributes to its better prognosis and improved management. This study aimed to quantify apoptotic cells in leukoplakia and oral squamous ...
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Background & Objective: Cell population and turnover are controlled by a balance between cell proliferation and apoptosis. Detection of apoptosis in oral cancer contributes to its better prognosis and improved management. This study aimed to quantify apoptotic cells in leukoplakia and oral squamous cell carcinoma (OSCC) using methyl green-pyronin (MGP) and hematoxylin and eosin (H & E) staining. Methods: The sample included a total of 130 subjects (comprising 108 males and 22 females). Formalin fixed and paraffin embedded tissues were used and categorized into three groups of normal oral mucosa (n=10), leukoplakia with dysplasia (n=60), and OSCC (n=60). The number of apoptotic cells and apoptotic index (AI) were calculated after staining with MGP and routine H & E stained slides. Results: MGP stained the condensed chromatin of apoptotic cells. Statistically significant difference (P≤0.001) was observed among various study groups in terms of numbers of AI and apoptotic cells. Also, AI increased with increasing grades of dysplasia, and it was the highest in well differentiated OSCC. Results were statistically significant in both H & E and MGP stained sections (P≤0.001). A good correlation was found between MGP and H & E staining results. Conclusion: MGP is more specific and can lead to intense staining for chromatin in apoptotic cells. Accordingly, it can provide a good alternative to H&E in identifying apoptotic cells.
Statistics
Zeinab Jozi; Hamzehali Nourmohammadi
Abstract
Background & Objective: This study examines the extent of scientific publications and patents in pathology and forensic medicine globally and the citation relationship between them from 2011 to 2020, indexed in the Scopus database.Methods: In this scientometric study, data were extracted from the ...
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Background & Objective: This study examines the extent of scientific publications and patents in pathology and forensic medicine globally and the citation relationship between them from 2011 to 2020, indexed in the Scopus database.Methods: In this scientometric study, data were extracted from the SciVal citation database. Search feature and library study method and annual growth rate, relative growth rate, and linear model were used to retrieve and analyze the data. The scientometric indicators included the number of publications and patents of the university in collaboration with industry, the number of articles cited by patents, the number of patents cited by articles, the average number of patents cited by articles, and the number of articles cited.Results: The results showed a poor collaboration between academia and industry in pathology and forensic Medicine, and North America is the busiest region in this field. The average growth of patents based on articles, the number of articles mentioned in patents, citations to patents, and the average number of patents of an institute in the articles of that institute have a positive exponential relationship. Based on the linear model, the relationship between articles and citations equals R2 = 0.982, which is inverse and negative. The data set of articles and citations was suitable for polynomial (R2 = .994), linear (R2= .982) and exponential (R2 = .887) models.Conclusion: The research process of pathology and forensic medicine is inappropriate, and the citation relationships between articles and patents in this field are weak. Strengthening the link between academia and industry in pathology and forensic medicine can strengthen research in this field.
Microbiology
Zahra Gholipour; Abbas Ali Imani Fooladi; Kazem Parivar; Raheleh Halabian
Abstract
Background & Objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when ...
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Background & Objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when cooperating with a specific vector. In this study, SEB was fused to interleukin-13 (IL13), which forms a complex with IL13 receptor α2 (IL13Rα2) overexpressed in glioblastoma multiforme (GBM) cells for therapeutic goals.Methods We designed four fusion proteins based on the arrangement of SEB (N- or C-terminal domain) and provided a flexible inter-domain linker (no or yes), resulting in the formation of SEB-IL13, SEB-L-IL13, IL13-SEB, and IL13-L-SEB, respectively. These fusion proteins were then evaluated for their various physicochemical properties and structural characteristics. Bioinformatics tools were employed to predict, refine, and validate the three-dimensional structure of the fusion proteins. In addition, the fusion proteins were docked with IL13Rα2, MHCII, and TCR receptors through the HADDOCK 2.4 server. The candidate fusion protein was subjected to molecular dynamics simulation.Results: There were differences among the designed fusion proteins. The model with the N-terminal domain of IL13 and containing an inter-domain linker (IL13-L-SEB) was stable and had a long half-life. The docking analysis revealed that the IL13-L-SEB fusion protein had a higher binding affinity to the IL13Rα2, MHCII, and TCR receptors. Finally, using molecular dynamics simulation through iMODS, acceptable results were obtained for the IL13-L-SEB docked complexes.Conclusion: The results suggest IL13-L-SEB is a promising novel fusion protein for cancer therapeutic application.
Neuropathology
Girish Solanke; Vidya Monappa; Ranjini Kudva
Abstract
Background & Objective: Meningiomas are the most frequently encountered primary non-glial tumors of the central nervous system (CNS). The Ki67 labelling index (Ki67LI) is a proliferation marker that may prove useful in determining the histological grade. This study aims at: 1) Studying the frequency, ...
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Background & Objective: Meningiomas are the most frequently encountered primary non-glial tumors of the central nervous system (CNS). The Ki67 labelling index (Ki67LI) is a proliferation marker that may prove useful in determining the histological grade. This study aims at: 1) Studying the frequency, grade and histomorphological spectrum of meningiomas, 2) Evaluating 20 histological parameters and determining its utility in grading meningiomas and 3) Comparing the Ki67LI in the various subtypes and WHO grades. Methods: The cases of meningiomas diagnosed in our Department from June 2009 to May 2014 were included. The clinical details, grade and 20 histological parameters: mitosis, vesicular nuclei, macronucleoli, nuclear pleomorphism, scattered bizarre nuclei, hypercellularity, sheeting, lymphocytes, small cell change, foam cells, ossification, necrosis, papillary change, lipidization, psammoma bodies, vascularization, brain invasion, dural invasion, bone invasion and other soft tissue invasion were recorded for each case. The average and highest Ki67LI was recorded as percentage and number per high power field. Results: A total of 175 cases of meningioma were included: grade I (145), grade II (30). Atypical histological features like hypercellularity, sheeting, etc. were common in grade II tumors. Increased vascularity, lymphocytes and psammoma bodies were common in grade I tumors. Ki67LI (highest) ranged from 1-6% in grade I and 5-12% in grade II tumors. Conclusion: Among different methods showing mitotic activity, Ki67% (highest) was the most statistically significant LI in differentiating grade I and grade II tumors. The median Ki67% (highest) was 4% for grade I and 7% for grade II tumors.
Gynecologic Pathology
Maryam Entezarian; Fereshteh Ameli; Noraidah Masir; Tan Geok Chin
Abstract
Background & Objective: Ovarian cancer is associated with the highest mortality rate among gynecologic malignancies. Despite new therapeutic strategies, ovarian cancer still has a high risk of metastasis and mortality. Endocan is a newly identified endothelial cell activation marker, which is responsible ...
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Background & Objective: Ovarian cancer is associated with the highest mortality rate among gynecologic malignancies. Despite new therapeutic strategies, ovarian cancer still has a high risk of metastasis and mortality. Endocan is a newly identified endothelial cell activation marker, which is responsible for angiogenesis, tumor invasion, and aggressive behavior of tumors. The aim of this study was to assess Endocan expression in different types of ovarian tumors and to identify its relationship with clinicopathologic characteristics of ovarian tumors.Methods: This cross-sectional study was conducted on 183 tissue samples, including benign, borderline, and malignant ovarian tumors collected from the University Kebangsaan Malaysia Medical Center archive of Pathology during 2005-2015. Mouse monoclonal anti-human Endocan/ESM-1 Clone MEP08 was used at a dilution of 1:400 for immunohistochemical (IHC) staining. All the information was collected by a checklist, and the association between clinicopathological features and high or low levels of Endocan -MVD was evaluated using Pearson chi-square, Fischer's exact, or Monte Carlo tests.Results: The prevalence of Endocan positivity was significantly higher in malignant compared to borderline and benign ovarian tumors (P<0.001). There was also a significant association between type of tumor and Endocan status in malignant ovarian tumors (P=0.02), indicating that Endocan positivity was more likely in serous malignant ovarian tumors compared to other ovarian tumor types. However, the tumor stage was not significantly associated with Endocan status (P=0.31).Conclusion: This study showed that Endocan positivity may show the highest prevalence among malignant tumors suggesting that high Endocan expression would be negatively associated with ovarian tumor behavior.
Bone & Soft tissue Pathology
Hadi Hassibi; Alireza Farsinejad; Shahriar Dabiri; Dariush Vosough; Abbas Mortezaeizadeh; Reza Kheirandish; Omid Azari
Abstract
Background & Objective:This study aimed to investigate the effect of decellularized allogeneic bone graft enriched by periosteal stem cells (PSCs) and growth factors on the bone repair process in a rabbit model, which could be used in many orthopedic procedures. Methods: In this experimental study, ...
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Background & Objective:This study aimed to investigate the effect of decellularized allogeneic bone graft enriched by periosteal stem cells (PSCs) and growth factors on the bone repair process in a rabbit model, which could be used in many orthopedic procedures. Methods: In this experimental study, a critical size defect (CSD) (10 mm) was created in the radial diaphysis of 40 rabbits. In group A, the defect was left intact with no medical intervention. In group B, the defect was filled by a decellularized bone graft. In group C, the defect was implanted by a decellularized bone graft enriched with platelet growth factors. In group D, the defect was treated by a decellularized bone graft seeded by periosteal mesenchymal stem cells (MSCs). Also, in group E, the defect was filled by a decellularized bone graft enriched with platelet growth factors and periosteal MSCs. Radiological evaluation was done on the first day and then in the second, fourth, and eighth weeks after the operation. The specimens were harvested on the 28th and 56th postoperative days and evaluated for histopathological criteria. Results: The radiologic and microscopic analysis of the healing process in bone defects of the treated groups (C, D, and E) revealed more advanced repair criteria than those of groups A and B significantly (P<0.05). Conclusion: Based on this study, it appears that implantation of concentrated PSCs in combination with growth factors and allogeneic cortical bone graft is an effective therapy for the repair of large bone defects.
Biology & Genetic
Seyedeh Elham Norollahi; Kosar Babaei; Vida Balooei; Seyed Masoud Hashemi Karouei; Mohammadtaghi Ashoobi; Elahe Asghari Gharakhyli; Ali Akbar Samadani
Abstract
Background & Objective: Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) ...
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Background & Objective: Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) and interleukin-6 (IL-6) is high and in severe cases of COVID-19, the production of IL-6, TNF-α, and other cytokines increases profoundly. On the other hand, investigating the molecular structure and receptors of IL-6 and TNFα and the structural analysis of the receptor proteins may potentially help to develop new therapeutic plans for COVID-19 infection.Methods: To identify genes with significant and different expressions in patients with COVID-19 in a microarray data set containing transcriptional profiles from GEO as a functional genomic database the GEO query package version 2.64.2 in a programming language R version 4.2.1 was downloaded. In this way, functional enrichment analysis for DEGs, WikiPathways, REGO, gene ontology, and STRING database was also investigated and employed.Results: The structure and function of pro-inflammatory cytokines TNFα and IL-6 involved in the pathogenesis of COVID-19 were investigated, and in general, after performing various analyses in this study and extracting A series of genes with different expressions from the KEGG database, the final 5 DEGs include CXCL14, CXCL6, CCL8, CXCR1, TNFRSF10, and the relationship and expression effects of them were observed in different pathways.Conclusion: IL-6 and TNFα were involved in immunological processes that had a direct and indirect relationship with the activation of cytokines, including IL6 and TNF-a, and cytokine storm, and this indicates their role in the formation of problems and complications, including ARDS, in COVID-19 patients. Of course, determining the effectiveness of each of these genes requires more specialized and clinical studies.
Oral Pathology
Hamideh Kadeh; Mohammad Eini; Maliheh Parsasefat; Ebrahim Miri-Moghaddam
Abstract
Background & Objective: CCL4 (C-C chemokine ligand4) is a chemoattractant involved in tumors' development, progression, and metastasis. The relationship between the ccl4 gene polymorphisms and the risk of OSCC has not been studied in Iran. This study aimed to identify the effect of ccl4 gene polymorphism ...
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Background & Objective: CCL4 (C-C chemokine ligand4) is a chemoattractant involved in tumors' development, progression, and metastasis. The relationship between the ccl4 gene polymorphisms and the risk of OSCC has not been studied in Iran. This study aimed to identify the effect of ccl4 gene polymorphism on OSCC susceptibility in the population of Southeastern Iran.Methods: In this case-control study, a total of 100 participants, 50 patients with OSCC who were referred to the Department of Oral Pathology, Faculty of Dentistry, Zahedan University of Medical Sciences, Iran, and 50 healthy people were included. The DNA was extracted from the tissue blocks of OSCC patients. The rs10491121 and rs1634507 in the ccl4 gene were evaluated by the tetra-ARMS (Amplification Refractory Mutation System)- PCR technique. Data were analyzed in SPSS (version 21) using the Chi-square and logistic regression test.Results: CCL4 genotyping showed that AA+AG genotype in rs10491121 and AA+CA genotype in rs1634507 were slightly higher in control than in the case. Still, the risk of OSCC in both polymorphisms was not significantly different. The minor allele (A) in the rs10491121 and rs1634507 polymorphisms were more common in OSCC compared to the control group (OR = 1.2, 95% CI: 0.66 – 2.22, P=0.54) (OR = 1.6, 95% CI: 0.85-3.07, P=0.15). There was no association between OSCC histopathological grades and CCL4 genotypes at these two sites.Conclusion: Our results showed no association between ccl4 gene polymorphism and the risk of oral cancer in the population of Southeastern Iran.
Gynecologic Pathology
Mohammad Hashemi-Bahremani; Abdolali Ebrahimi; Mohaddese Fallahi
Abstract
Background & Objective: The her2 amplification plays an important role in breast cancer management. Therefore, there is a need for using supplementary molecular methods in IHC equivocal cases. Present study has been conducted to determine the effects of clinicopathological variables on her2 gene ...
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Background & Objective: The her2 amplification plays an important role in breast cancer management. Therefore, there is a need for using supplementary molecular methods in IHC equivocal cases. Present study has been conducted to determine the effects of clinicopathological variables on her2 gene amplification by chromogenic in situ hybridization (CISH) in IHC Her2 (2+) breast cancer individuals. Methods: A cross-sectional study was conducted in Zaferanyeh Laboratory collaborated with Shahid Beheshti University of Medical Sciences (Tehran-Iran; 2015-2018). All pathological data related invasive breast cancer patients with equivocal IHC results were included. CISH method was performed as a supplementary technique. The associations between histopathologic variables, status of Ki-67 index, progesterone and estrogen receptors (PR & ER) with her2 amplification by CISH were investigated and analyzed. The level of significance was considered as P-value < 0.05. Result: Totally, 239 patients with mean age of 53.2 years were studied. CISH identified her2 gene amplification in 51 subjects (21.3%). The type of tumor (invasive ductal carcinoma), the tumor grade, and the value of Ki-67 index were directly correlated with her2 amplification. Significant negative associations were also observed between CISH results and ER and PR expression. Conclusion: As her2 gene amplification was identified in 21.3% of invasive breast cancer patients with equivocal IHC results, it is supposed that applying CISH method may consider as a potentially valuable supplementary method. Results have also shown that higher grades of tumor, invasive ductal carcinoma, absences of hormone receptors and high Ki-67 index significantly correlated with the her2 amplification.
Breast Pathology
Swaminathan Kalyanasundaram; Shantaraman Kalyanaraman; Hidhaya Kaleelullah Fathima; Vidhya Mohan; Kavitha Selvaraj
Abstract
Background & Objective: Triple-Negative Breast Carcinoma (TNBC) is characterized by an absence of estrogen receptor, progesterone receptor and HER2 neu expression, with distinct molecular, histological and clinical features, aggressive clinical course and a poor prognosis. The objective was to evaluate ...
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Background & Objective: Triple-Negative Breast Carcinoma (TNBC) is characterized by an absence of estrogen receptor, progesterone receptor and HER2 neu expression, with distinct molecular, histological and clinical features, aggressive clinical course and a poor prognosis. The objective was to evaluate the expression of Cytokeratin5/6 (CK 5/6), Epidermal Growth Factor Receptor 1 (EGFR 1), E-cadherin and Androgen receptor in tissue sections of TNBC.Methods: All modified radical mastectomy samples received negative for the three markers were subjected to further studies with CK5/6, EGFR 1, E- cadherin and Androgen receptor staining. The clinical and pathological data were tabulated and statistically analysed using the Chi-square test, and cross-tabulation was done to assess the correlation between these markers.Results: Of 94 samples classified as TNBC, 31 (33%) were positive for CK 5/6, 47 (50%) for EGFR, 32 (34%) for E Cadherin and Androgen receptor, respectively. We had one positive patient for all four markers, 13 patients were negative for all four. Thirty-five cases were positive for only one marker, 32 were positive for two markers, and 13 were positive for three markers. Analysis revealed certain interesting patterns, namely - E cadherin was the most common isolated marker expressed in our cohort of TNBC with 15 of 35 positives.Conclusion: This study highlights the presence of a unique subtype of TNBC, which are negative for all the four markers studied here, with unique histomorphology of absent tumour necrosis and stromal lymphocytic infiltration being unique.
Gynecologic Pathology
Elham Mirzaian; Tahereh Doustmohammadi; Mahshid Panahi; Soheila Sarmadi; Fereshteh Ameli; Fatemeh Nili
Abstract
Background & Objective: GATA3 immunohistochemistry has been described as a highly sensitive marker in determining carcinomas of breast and urothelial origin. In the gynecologic system, it can be used as a marker to diagnose mesonephric or mesonephric-like carcinomas and trophoblastic tumors. The ...
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Background & Objective: GATA3 immunohistochemistry has been described as a highly sensitive marker in determining carcinomas of breast and urothelial origin. In the gynecologic system, it can be used as a marker to diagnose mesonephric or mesonephric-like carcinomas and trophoblastic tumors. The present study was performed to determine the diagnostic value of GATA3 in gynecological adenocarcinomas.Methods: A total of 187 samples from different types of endometrial, endocervical, and ovarian carcinomas were analyzed for intensity and percentage of GATA3 expression in tumor cells. The relationship between GATA3 expression and clinicopathological parameters was investigated.Results: A total of 187 patients including 101 ovarian, 77 endometrial, and 9 endocervical adenocarcinomas were investigated. Weak and focal expression of this marker was observed in 5. 1% (4/77) endometrial, 12.9% (13/101) ovarian, and 11.1% (1/9) endocervical adenocarcinomas. The mean H score in all subtypes was less than 10.6 (2-35). There was no statistically significant correlation between GATA3 expression in tumor cells with clinical stage, and tumor recurrence or metastasis.Conclusion: GATA3 is infrequently, weak, or focally expressed in most of the common gynecological adenocarcinomas.
Molecular Pathology
Armin Attar; Mohsen Khosravi Maharlooei; Mohammad Nazarnia; Ahmad Hosseini; Zohre Bajalli; Yalda Sadat Moeini; Ahmad Monabati; Fatemeh Amirmoezi; Mansooreh Jaberipour; Mojtaba Habibagahi
Abstract
Background & Objective: It is not clear whether activated lymphocytes of patients with systemic lupus erythematosus (SLE) are more proliferative or less apoptotic. We aimed to delineate potential differences between B and T cells of SLE patients compared to healthy controls regarding the telomerase ...
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Background & Objective: It is not clear whether activated lymphocytes of patients with systemic lupus erythematosus (SLE) are more proliferative or less apoptotic. We aimed to delineate potential differences between B and T cells of SLE patients compared to healthy controls regarding the telomerase activity and apoptosis status. Methods: In this cross-sectional case control study, Blood samples were taken from 10 SLE patients and 10 healthy controls. B and T cells were separated using magnetic cell sorting system. Telomeric repeat amplification protocol (TRAP) assay and real-time PCR were used to determine the telomerase activity and the expression of alternatively spliced variants. Result: Four patients under treatment showed significant telomerase activity in their T cells. Four of the newly diagnosed patients showed telomerase activity in their B cells (20% of all patients and 40% of new onset patients). There was no specific pattern of human telomerase reverse transcriptase variant expression within the patients’ lymphocytes. A significantly reduced expression of Bcl-2 was detected in B cells (P=0.018) and a trend toward lower Bcl-2 expression in T cells was seen in SLE patients compared to healthy controls. Conclusion: Although not definitive, our results may suggest that B cells may have more active roles during the earlier phases of the disease attack, while T cells take over when the disease reaches its chronic stages.
Endocrine Pathology
Vahid Zand; Mansour Moghimi; Elmira Sadeghi; Pegah Kamal; Sedighe Vaziribozorg
Abstract
AbstractPapillary thyroid carcinoma (PTC) is considered as a relatively common type of malignancy showing a wide morphologic spectrum. Different variants of this tumor have been reported. Among PTC variants, PTC with nodular fasciitis-like stroma (PTC‑FLS) is rare. This variant consists of stromal ...
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AbstractPapillary thyroid carcinoma (PTC) is considered as a relatively common type of malignancy showing a wide morphologic spectrum. Different variants of this tumor have been reported. Among PTC variants, PTC with nodular fasciitis-like stroma (PTC‑FLS) is rare. This variant consists of stromal components rich in spindle cells and accounts for 60-80% of tumors. In addition, there are small foci of epithelial components in PTC‑FLS though its features are similar to conventional PTC. In this case study, we present a new case with PTC‑FLS. The case is a 28-year-old female who was referred to the ENT clinic due to a painless mass on the anterior part of her neck. The mass showed a gradual increase in size over the 6 months prior to her referral. Thyroid test results were normal. Ultrasound imaging demonstrated an 84 × 36 mm heterogeneous nodule in the right thyroid lobe without calcifications but increased vascularity. There were also some reactive lymph nodes in both sub-mandibular areas. An ultrasound-guided fine-needle aspiration (FNA) biopsy of the right thyroid lobe nodule revealed a benign thyroid adenomatoid nodule. Following right thyroid lobectomy, final pathologic studies confirmed a diagnosis of PTC with exuberant fibromatosis-like stroma. In the 20-day post-surgery visit, the patient was found asymptomatic. Re-evaluation of the left thyroid lobe and follow-up were recommended. In this study, a diagnosis of a rare variant of PTC, i.e., PTC-FLS, was made through a combination of ultrasonography, fine needle aspiration cytology, and histological examination.
Gynecologic Pathology
Kavita Gaur; Shailaja Shukla; Shinjini Choudhury; Pankaj Raj; Sharda Patra
Abstract
Uterine leiomyoma with hepatic vasculopathy, specifically non-cirrhotic portal fibrosis (NCPF), has hitherto been undescribed. NCPF is characterized by elevated portal pressure sans cirrhosis and has previously not been described in association with a gynecological pathology. We report the case of a ...
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Uterine leiomyoma with hepatic vasculopathy, specifically non-cirrhotic portal fibrosis (NCPF), has hitherto been undescribed. NCPF is characterized by elevated portal pressure sans cirrhosis and has previously not been described in association with a gynecological pathology. We report the case of a female under evaluation for a heterogeneously enhancing intrauterine mass with multiple hepatic lesions with increased uptake of fluorodeoxyglucose on positron emission analysis. Fibroscan values were increased. Histopathologic evaluations revealed a leiomyoma with liver tissue showing tubercular granulomas, thin wispy fibrotic strands, and rounded portal tracts pointed to NCPF. No evidence of malignancy was seen. Metabolic imaging may be unreliable to distinguish between benign and malignant uterine pathology and granulomatous and malignant hepatic lesions. Elastography may also be ineffective in diagnosing the etiology of liver fibrosis. Histopathological analysis hence remains essential despite noninvasive tests. Further research is required on females afflicted with NCPF to exclude a hormonal link.
Uropathology
Marwa Mohammed Dawoud; Noha Elkady; Rasha Adel Abdelmoneum; Ahmed S Ghonaimy; Dina Mohamed Allam
Abstract
Background & Objective: Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical ...
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Background & Objective: Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical biomarkers becomes mandatory. This study aims to investigate P4HB and SOX4 expression in prostatic carcinoma, their possible roles, and clinical significance.Methods: This retrospective study included fifty-six cases of PAC and an equal number of nodular prostatic hyperplasia (NPH) that were immunohistochemically stained by P4HB and SOX4. The results of expression were compared between PAC and NPH cases, followed by correlations with available clinicopathological parameters.Results: There was a highly significant difference between PAC and NPH regarding P4HB and SOX4 expressions in favor of PAC (both P<0.001). ROC curve analysis of the diagnostic power of P4HB showed 79% sensitivity, 76% specificity, 76.5%, and an area under the ROC curve of 0.845, while SOX4 showed (89%, 100%, and 0.946, respectively). P4HB and SOX4 expression showed a direct correlation (P<0.001). Moreover, SOX4 showed a significant inverse relation with ERG (P=0.047). There was a significant correlation between P4HB and SOX4 and Gleason score (P<0.001). Moreover, P4HB expression was significantly associated with lymphovascular invasion (P=0.013), while SOX4 expression showed a significant association with perineural invasion (P=0.05).Conclusion: SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected.
Uropathology
Ikram A. Hasan; Hiba Gaidan; Methaq Al-kaabi
Abstract
Background & Objective:Some prostatic lesions contain small suspicious foci for prostatic carcinoma in which the morphological features are equivocal. Two immunohistochemical markers namely, cytokeratin 34 beta E12 (Ck34βE12) and α-Methylacyl-CoA racemase (AMACR), were evaluated in these ...
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Background & Objective:Some prostatic lesions contain small suspicious foci for prostatic carcinoma in which the morphological features are equivocal. Two immunohistochemical markers namely, cytokeratin 34 beta E12 (Ck34βE12) and α-Methylacyl-CoA racemase (AMACR), were evaluated in these lesions for a definitive diagnosis and avoiding misdiagnosis or overdiagnosis of prostatic carcinoma. Methods:A total of 90 paraffin embedded blocks of prostatic tissue were selected and categorized into three groups as follows: 50 cases of benign prostatic hyperplasia (BPH), 20 cases of prostatic carcinoma, and 20 cases of benign prostatic lesions with suspicious foci labeled as ASAP (atypical small acinar proliferation) that occupy not more than 5% of the lesion. These cases were revised for histopathological diagnosis and stained with two immunohistochemical markers: Ck34βE12 and AMACR. Result:While 92.9% of BPH were positive for Ck34βE12, 96% of prostatic carcinoma were negative for this marker (P=0.0001). Regarding AMACR, 92.9% of BPH cases were negative, but 92% of prostatic carcinoma cases were positive for this marker (P=0.0001). Out of 20 cases of BPH, 15 cases containing suspicious foci showed Ck34βE12+/AMACR- (diagnosis: benign), but 5 cases were Ck34βE12-/AMACR+, for which the diagnosis changed to prostatic carcinoma (P=0.04). Conclusion :Immunohistochemical staining with Ck34βE12 and AMACR improved the diagnostic performance and also increased confidence level for establishing definite diagnosis in cases with suspicious foci, in which the morphological features were equivocal. This could help to avoid misdiagnosis or overdiagnosis of prostatic carcinoma that would eventually improve the management of the patient and subsequently the prognosis.
Dermatopathology
Faezeh Taghavi; Sima Davoodi; Naser Tayyebi Meibodi; Yalda Nahidi; Mostafa Izanlu
Abstract
Nevus comedonicus (NC) is a rare developmental anomaly of the folliculosebaceous apparatus, which appears as numerous dilated papules containing firm, darkly pigmented, horny plugs. It appears shortly after birth and mostly before the age of 10; however, late-onset cases have been reported. There is ...
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Nevus comedonicus (NC) is a rare developmental anomaly of the folliculosebaceous apparatus, which appears as numerous dilated papules containing firm, darkly pigmented, horny plugs. It appears shortly after birth and mostly before the age of 10; however, late-onset cases have been reported. There is no gender or racial predilection. Moreover, NC can be a component of nevus comedonicus syndrome, a neurocutaneous disorder with skeletal, ocular, and central nervous system abnormalities. EHK properties in NC are not a common finding and are rarely seen in association with each other. This paper reports a healthy, 27-year-old young woman who has been developing numbers of asymptomatic unilateral linear skin lesions on her chest, waist, right thigh, and popliteal fossa in a unilateral linear pattern over ten years. Skin biopsy revealed dilated follicular ostia with orthokeratotic hyperkeratosis, columns of parakeratosis, cornoid flagellation, epidermolytic hyperkeratosis, and mild acanthosis on its wall.
Oral Pathology
Vaishnavi Vedam; Sivadas Ganapathy
Abstract
Dear EditorHead and Neck Cancers (HNCs) contribute to one of the global health concerns and have been a challenge to oncologists for decades. Breakthroughs in research with evidence-based reports based on diagnostic and therapeutic approaches in clinical practice have been published to address patient ...
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Dear EditorHead and Neck Cancers (HNCs) contribute to one of the global health concerns and have been a challenge to oncologists for decades. Breakthroughs in research with evidence-based reports based on diagnostic and therapeutic approaches in clinical practice have been published to address patient concerns. Risk factors, namely age, sex, diet, habits, and geographical variations, pose an established link with the prevalence of HNCs. Despite ongoing studies in cancer, the 5-year survival rate of the patients remains <50% to date. This has encouraged the scientists to research other possible novel risk factors and prognosis transformers that could present as targets for preventive or therapeutic interventions.
Breast Pathology
Azar Naimi; Maryam Sultan; Elham Amjadi; Parvin Goli; Amirhosein Kefayat
Abstract
Background & Objective: Our knowledge about correlation of androgen receptor expression and clinicopathological properties of triple-negative breast cancer (TNBC) patients is inadequate, particularly in the Iranian population. The main aim of the present study was to assess the AR expression in TNBC ...
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Background & Objective: Our knowledge about correlation of androgen receptor expression and clinicopathological properties of triple-negative breast cancer (TNBC) patients is inadequate, particularly in the Iranian population. The main aim of the present study was to assess the AR expression in TNBC Iranian patients and evaluate its correlation with their clinicopathological parameters. Methods: Herein, 76 TNBC patients were evaluated for the AR expression by immunohistochemistry. The slides' staining intensity was investigated according to the average degree of nuclear staining and sub-classified into negative (0), weak (1), moderate (2), or strong (3). Subsequently, the positive cells percentage for each slide was assessed and sub-classified into <25% (1), 25-50% (2), 50-75% (3), and >75% (4). The aggregation of these two scores was used as the final score ranging from 0 to 7. While 4-7 scores were selected as positive, the others were included in the AR-negative expression group. Fisher's exact test was used to analyze the AR expression correlation with the clinicopathological parameters. Result : Positive immunoreactivity for AR was observed in 8 out of 76 (11%) specimens. No-correlation (P>0.05) was observed between the AR expression and grade, stage, lymph node status, and Ki-67 level. The AR-positive patients exhibited older age at the time of diagnosis (P=0.0339) and larger tumor size (P=0.0224) in comparison with the AR-negative patients. Low percentage of TNBC patients expressed AR and no significant correlation was observed between its expression and most of the clinicopathological parameters. Conclusion : AR may not be a suitable biomarker and treatment target for the Iranian patients with TNBC.
