Molecular Pathology
Mohammad Vaseie; Mahsa Soti Khiabani; Maryam Monajemzadeh; Hojatollah Raji; Fatemeh Zamani; Neda Pak
Abstract
The occurrence of rectosigmoid junction inflammatory myofibroblastic tumor IMT is uncommon in children. This is a rare form of mesenchymal tumor, belonging to the category of soft tissue tumors, and can be found at any anatomical site from the central nervous system to the gastrointestinal tract.Our ...
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The occurrence of rectosigmoid junction inflammatory myofibroblastic tumor IMT is uncommon in children. This is a rare form of mesenchymal tumor, belonging to the category of soft tissue tumors, and can be found at any anatomical site from the central nervous system to the gastrointestinal tract.Our patient was a 10-year-old male subject complaining of lack of defecation and constipation. The patient had decreased the frequency of defecation and constipation about two weeks before his referral and had not improved despite the use of laxatives. The abdomen was completely distended and there was no tenderness or guarding in the examination. Several airfluid levels are shown on the abdominal X-ray. In the ultrasound, free fluid was reported in the interlobular and pelvic spaces. The patient was transferred into the operating room. A tumor of the rectosigmoid junction was detected. The pathology showed evidence of IMT.IMT is a rare neoplastic tumor of unknown origin which may be present at various sites in the body. Complete surgical removal is usually curative, but early detection of recurrence is required. Treatment options include chemotherapy, radiation therapy, and immunotherapy, and further research is needed to improve the understanding and management of this rare tumor.
Molecular Pathology
Sarah Siahbani; Akbar Safaie; Masoumeh Faghih; Marzieh Hosseini; Afsaneh Fendereski; Behnaz Valibeigi; Ahmad Monabati
Abstract
Background & Objective: Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(15;17)(q22;q21)), leading to the formation of the PML-RARA fusion gene with three possible isoforms. This study aims to ...
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Background & Objective: Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(15;17)(q22;q21)), leading to the formation of the PML-RARA fusion gene with three possible isoforms. This study aims to investigate the characteristics of Iranian APL patients, the distribution of PML-RARA isoforms, and survival analysis.Methods: We included 145 consecutive eligible patients in this study. Data were collected through archived documents and phone inquiries, following consent. Subsequently, we analyzed the data using SPSS software version 26.0.Results: We examined 75 men and 70 women, with a mean age of 34 years (range: 2-78 years). Besides t(15;17) (q22;q21), 45.6% had other chromosomal abnormalities. The prevalence of bcr1 and bcr3 isoforms was 73% and 27%, respectively. bcr3 correlated with higher white blood cell (WBC) counts, additional chromosomal abnormalities, and faster Complete Hematologic Response (CHR). Early death occurred in approximately 36% of all patients. The mean overall survival time was 73.5 months, with 120-month survival rates of 53.8% for all patients and 83.9% for those who achieved CHR. Univariate analysis identified old age, relapse, lower platelet (PLT) counts, higher WBC counts, and leukocytosis as survival risk factors. However, in multivariate analysis, only old age and higher WBC counts were identified as adverse prognostic factors.Conclusion: In Iranian APL patients, bcr1 predominates, while bcr3 correlates with higher WBC counts, high-risk categorization, additional chromosomal abnormalities, and faster CHR. Survival is negatively impacted by old age, relapse, lower PLT counts, higher WBC counts, and leukocytosis.
Molecular Pathology
Amirhossein Jafarian; Masoumeh Jafaripour; Masoumeh Gharib; Maryam Salehi; Nema Mohamadian Roshan; Sare Etemad; Khatoone Mirshekar; Maryam Sheikhi; Masoumeh Heidari; Behnaz Ahmadian; Zahra Khoshnegah; Hossein Ayatollahi; Payam Siyadat
Abstract
Background & Objective: Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progress of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling ...
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Background & Objective: Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progress of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes.Methods: A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing.Results: While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma (P=0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group.Conclusion: The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.
Molecular Pathology
Fatemeh Hoseini Tabatabaie; Seyed Younes Hosseini; Seyed Mohammad Ali Hashemi; Akbar Safaie; Jamal Sarvari
Abstract
Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical ...
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Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical and ovarian cancer and healthy individuals.Methods: As test and control groups, 18 EBV-positive paraffin-embedded samples of cervical and ovarian cancer and 10 age- and gender-matched healthy volunteers who did not have cancer but were EBV-positive were both used. Utilizing a commercial DNA extraction kit, total DNA was extracted following deparaffinization. The entire C-terminal region of the EBNA1 sequence was amplified using an in-house nested PCR. Phylogenetic analysis and Sanger sequencing were used to analyze the sequences using MEGA 7 software and through NJ method.Results: Sequence analysis revealed that the P-Ala subtype of EBNA1 was present in all samples. In two and one samples, respectively, of cervical cancer patients, the mutations A1887G and G1891A were found. The G1595T mutation was also detected in four sequences taken from ovarian cancer patients. No statistically significant difference could be found between the frequency of mutations in patients and controls (P>0.05). No known amino acid substitutions were found in the USP7-binding region and the DBD/DD domain.Conclusion: The findings showed that P-Ala is the predominant EBV subtype across all samples. Additionally, as the sequence of EBNA1's C-terminal region is so stable, it's possible that it had little impact on the pathogenesis of ovarian and cervical malignancies. It is advised to conduct additional research to verify these findings.
Molecular Pathology
Aparna Devi C; Ashwini Nargund; Geeta V Patil Okaly; Usha Amirtham
Abstract
Angiomatoid Fibrous histiocytoma (AFH) is a rare soft tissue neoplasm that is often misdiagnosed initially. It is commonly encountered in the superficial extremities of children and young adults. It is composed of a nodular proliferation of bland looking spindled to ovoid cells, some with variant histology ...
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Angiomatoid Fibrous histiocytoma (AFH) is a rare soft tissue neoplasm that is often misdiagnosed initially. It is commonly encountered in the superficial extremities of children and young adults. It is composed of a nodular proliferation of bland looking spindled to ovoid cells, some with variant histology and characterized by EWSR1 fusion. We, herein, present three such cases, who presented with swelling in the right leg (case 1), right forearm (case 2), and right thigh (case 3). Case 2 presented in the fourth decade with a large swelling compared to the other two cases that presented in 3rd decade with a small swelling. Histologic examination of case 2 showed extensive myxoid changes making it diagnostically challenging. All three cases showed EWSR1 fusion with a break-apart probe. Follow-up was uneventful in all three cases. AFH, although it is a benign neoplasm, is a great mimicker of various low-grade spindle cell sarcomas. Awareness of this entity with its various histomorphological variants is necessary to accurately diagnose this lesion.
Molecular Pathology
Seyed Amir Miratashi Yazdi; Elham Nazar
Abstract
The etiology of parathyroid carcinoma (PC) is largely unknown. Associations have been made with several inherited syndromes and with specific genetic lesions. The management of PC is challenging for clinicians. The complexity of molecular phenotypes increases with tumor aggressiveness. Lack of parafibromin ...
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The etiology of parathyroid carcinoma (PC) is largely unknown. Associations have been made with several inherited syndromes and with specific genetic lesions. The management of PC is challenging for clinicians. The complexity of molecular phenotypes increases with tumor aggressiveness. Lack of parafibromin on immunohistochemistry staining and HRPT2 mutation present capable consequences in differentiating carcinoma from adenoma. Lack of parafibromin expression, the gene product of HRPT2 is now used as a diagnostic, prognostic and predictive marker for parathyroid carcinoma. The epigenetic alteration, for example, DNA methylation and modifications in the chromatin structure, are known as significant events that are the reason for parathyroid tumorigenesis. We suggest that adjuvant genetic and epigenetic target therapy should be considered in treating PC patients.
Molecular Pathology
Alireza Rastgoo Haghi; Nasrin Khorami; Mahtab Fotoohi; Abbas Moradi
Abstract
Background & Objective: Diabetes is a metabolic disease and is associated with failure of various organs. Macrophage migration factor (MIF) and matrix metalloproteinase (MMP-9) are two of the most important factors in the pathogenesis of diabetes.Methods: In this descriptive-analytical study, 30 ...
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Background & Objective: Diabetes is a metabolic disease and is associated with failure of various organs. Macrophage migration factor (MIF) and matrix metalloproteinase (MMP-9) are two of the most important factors in the pathogenesis of diabetes.Methods: In this descriptive-analytical study, 30 patients with type 2 diabetes mellitus from Hamadan Diabetes Center were selected by convenience sampling. Moreover, 30 healthy first-degree relatives and 30 unrelated non-diabetics, were examined for MMF and MMP-9 and their variations based on age, gender, body mass index (BMI) and hemoglobin A1C.Results & Conclusion: The mean and standard deviation of MIF in diabetic patients, and relatives and non-relatives of diabetic patients were 592.87±78.19, 131.82±88.27 and 94.63±23.88, respectively (P<0.001). The mean and standard deviation of the MMP-9 in diabetic patients, and relatives and non-relatives of diabetic patients were 2570.64±2220.03, 918.57±650.08 and 629.09±288.32, respectively (P<0.001). MIF and MMP-9 did not have a significant relationship with age, sex, duration of disease and BMI. However, we observed a direct and significant correlation between hemoglobin A1C and the level of MIF and MMP-9 (P<0.001). In patients with type 2 diabetes, serum levels of MMP-9 and MIF, consistent with HbA1c, increase with no significant association with age, sex, BMI and duration of diabetes.
Molecular Pathology
Maryam Sotoudeh Anvari; Atoosa Gharib; Maryam Abolhasani; Aileen Azari-Yaam; Farzaneh Hossieni Gharalari; Moeinadin Safavi; Ali Zare-Mirzaie; Mohammad Vasei
Abstract
Molecular assays for detection of nucleic acids in biologic specimens are valuable diagnostic tools supporting clinical diagnoses and therapeutic decisions. Pre-analytical errors, which occur before or during processing of nucleic acid extraction, contribute a significant role in common errors which ...
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Molecular assays for detection of nucleic acids in biologic specimens are valuable diagnostic tools supporting clinical diagnoses and therapeutic decisions. Pre-analytical errors, which occur before or during processing of nucleic acid extraction, contribute a significant role in common errors which take place in molecular laboratories. Certain practices in specimen collection, transportation, and storage can affect the integrity of nucleic acids before analysis. Applying best practices in these steps, helps to minimize those errors and leads to better decisions in patient diagnosis and treatment. Widely acceptable recommendations, which are for optimal molecular assays associated with pre-analytic variables, are limited. In this article, we have reviewed most of the important issues in sample handling from bed to bench before starting molecular tests, which can be used in diagnostic as well as research laboratories. We have addressed the most important pre-analytical points in performing molecular analysis in fixed and unfixed solid tissues, whole blood, serum, plasma, as well as most of the body fluids including urine, fecal and bronchial samples, as well as prenatal diagnosis samples.
Molecular Pathology
Zohreh Rahimi; Maryam Bozorgi Zarini Bozorgi Zarini; Ziba Rahimi; Ebrahim Shakiba; Asad Vaisi-Raygani; Mohammad Taher Moradi; Kheirolah Yari
Abstract
Background & Objective: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism (OCM) disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine ...
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Background & Objective: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism (OCM) disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC.Methods: The present case-control study consisted of 100 BC patients and 141 healthy females. The TYMS 2R/3R (rs34743033), MTR c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively.Results: The 3R allele of TYMS enhanced the risk of BC by 2.84-fold (p <0.001). In the presence of TYMS 3R/3R, compared to TYMS 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, p =0.055). The frequencies of MTR c.2756A>G and MTRR c.66A>G variants were not significantly different among patients and controls.Conclusion: We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele tends to increase the BC metastasis.
Molecular Pathology
Mitra Heidarpour; Mehran Taheri; Ali Akhavan; Parvin Goli; Amirhosein Kefayat
Abstract
Background & Objective: Human epidermal growth factor receptor 2 (HER-2) exhibits a vast range of expression in esophageal squamous cell carcinoma (ESCC) patients as a biomarker. This paper aimed to investigate HER-2 expression and clinicopathological parameters of esophageal SCC. Methods: HER-2 ...
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Background & Objective: Human epidermal growth factor receptor 2 (HER-2) exhibits a vast range of expression in esophageal squamous cell carcinoma (ESCC) patients as a biomarker. This paper aimed to investigate HER-2 expression and clinicopathological parameters of esophageal SCC. Methods: HER-2 expression was assessed in 102 ESCC patients by immunohistochemistry. The HER-2 staining intensity , according to the Gastric HER2 Biomarker1.0.0.1 version of the college of American pathologists (CAP) protocol for gastric and gastroesophageal junction cancers, was graded as 0 (no reactivity in any of the cancer cells’ membranes); 1+ (pale or hardly noticeable reactivity in the membrane of cancer cells’ cluster [≥ 5 neoplastic cells] regardless of the positive cancer cells’ percentage); 2+ (weak-to-moderate complete, basolateral, or lateral membranous reactivity regardless of the positive cancer cells’ percentage); and 3+ ( strong complete, basolateral, or lateral reactivity in the membrane of the cancer cell cluster regardless of the positive cancer cells’ percentage).In this regard, 3+ scored samples were considered as positive. If HER-2 expression was scored 2+, an additional fluorescence in situ hybridization (FISH) was performed. Fisher's exact test was employed for investigating the correlation of HER-2 expression status with patients’ clinicopathological characteristics (including age, gender, tumor location, stage, grade, infiltration level, venous invasion, lymphatic invasion, and tumor recurrence). Kaplan-Meier analysis was done for the patients’ survival assessments. Result: Five patients (~5%) were HER-2 positive and no significant association was observed between HER-2 expression and clinicopathological properties. In addition, HER-2 expression status exhibited no significant association with the patients’ overall survival (p =0.9299). Conclusion: HER-2 is not a suitable prognostic biomarker for Iranian ESCC patients.
Molecular Pathology
Alireza Abdollahi; Abbas Shakoori; Hoda Khoshnevis; Mohammad Arabzadeh; Seyed Ali Dehghan Manshadi; Esmaeil Mohammadnejad; Dorsa Ghasemi; Maryam Safari Aboksari; Shaban Alizadeh; Vahid Mehrtash; Arezoo Eftekhar-javadi; Masoomeh Safaei
Abstract
Background & Objective: A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study ...
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Background & Objective: A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study was to compare lab technician- with patient- collected oropharyngeal and nasopharyngeal samples for detection of the coronavirus disease 2019 (COVID 19) using rapid real-time polymerase chain reaction (rRT-PCR). Methods: Fifty adult patients with flu-like symptoms and radiologic findings compatible with atypical pneumonia who were admitted to the infectious diseases ward of Imam Khomeini Hospital Complex, Tehran, Iran, with a clinical diagnosis of COVID-19 from February 28 to April 27 of 2020 were randomly selected and entered in our study. Two sets of naso- and oropharyngeal swabs were collected, one set by a lab technician and the other by the patients, and the COVID-19 rRT-PCR test was performed. Results: Of 50 selected cases, in seven patients all collected naso- and oropharyngeal swabs tested positive, and in 22 patients all samples tested negative for COVID-19 in rRT-PCR. Discrepancies between rRT-PCR results of lab technician- and patient-collected swabs were observed in 12 nasopharyngeal and 13 oropharyngeal specimens. Positive lab technician-collected and negative patient-collected samples were observed in 10 and 5 nasopharyngeal and oropharyngeal specimens, respectively. Negative lab technician-collected and positive patient-collected samples were observed in two and seven nasopharyngeal and oropharyngeal specimens, respectively. The overall percentage of agreement among both nasopharyngeal and oropharyngeal swabs taken by a lab technician and patients was 76% with a kappa value of 0.49 (p =0.001). Conclusion: Based on our findings, lab technician-collected naso- and oropharyngeal swabs cannot be replaced by patient-collected ones with regard to COVID-19 rRT-PCR.
Molecular Pathology
Mahdieh Mahboobi; Reza Mirnejad; Hamid Sedighian; Vahhab Piranfar; Abbas Ali Imani Fooladi
Abstract
Background & Objective: Vibrio cholerae is a natural inhabitant of the environment and causes severe diarrhea ailments (cholera) that affects thousands of people each year worldwide. The most important virulence factors of this pathogen are cholera toxin (cholera toxin CT) and Type IV ...
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Background & Objective: Vibrio cholerae is a natural inhabitant of the environment and causes severe diarrhea ailments (cholera) that affects thousands of people each year worldwide. The most important virulence factors of this pathogen are cholera toxin (cholera toxin CT) and Type IV pili (toxin co-regulated pili TCP), which are encoded within the genome of the filamentous bacteriophage CTXφ. In the present study, according to researchers’ report on genotypic variations of cholera toxin, we evaluated the sequence of ctxB subunit obtained from 100 strains of patients infected with cholera in Iran. Methods: The evaluation of genotype variations of cholera toxin was made by high-resolution melting curve analysis illustrating a single nucleotide change. Then, ctxB gene sequencing was performed. Through this analysis and the sequencing process, two standard samples were studied. Results: Using serologic tests, all the strains analyzed in this study were identified to be in O1 serotype. However, there have been differences in sequences of ctxB as some were similar to V. cholerae O1 biovar El Tor str. N16961 while others were similar to the genotype of V. cholerae ATCC 14035. We did not observe any particular pattern within the process of mutation. Conclusion: The analysis of the new samples of ctxB showed that they were potentially different. It seems that these complicated species were affected by a new genetic exchange of El Tor and classic genotypes.
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.
Molecular Pathology
Amir Hossein Jafarian; Nema Mohammadian Roshan; Hossein Ayatollahi; Abbas Ali Omidi; Masoumeh Ghaznavi; Masoumeh Gharib
Abstract
Background & Objective:Idiopathic pulmonary fibrosis (IPF) is a chronic and uniformly fatal interstitial lung disease with incompletely understood pathogenesis. Several studies have given the evidence for and against viral cofactors in the pathogenesis of Idiopathic pulmonary fibrosis. In this study ...
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Background & Objective:Idiopathic pulmonary fibrosis (IPF) is a chronic and uniformly fatal interstitial lung disease with incompletely understood pathogenesis. Several studies have given the evidence for and against viral cofactors in the pathogenesis of Idiopathic pulmonary fibrosis. In this study Epstein-Bar Virus (EBV) and Human Herpesvirus 8 (HHV-8) have been studied for a possible role in the pathogenesis of IPF.Methods:Polymerase chain reaction (PCR) was employed for the detection of EBV and HHV-8 in 58 formalin-fixed paraffin-embedded lung tissue specimens (29 controls and 29 IPF specimens).Results:EBV DNA was present in the lung tissue of 6 out of 29 (20.7%) IPF specimens compared with 1 out of 29 (3.4%) controls (P=0.102). The HHV-8 gene was identified in 3 out of 29 (10.3%) cases of IPF specimens. The control group showed no evidence of HHV-8 gene (P=0.227).Conclusion:Although multiple studies are strongly suggestive of a role for EBV and HHV-8 in the development of IPF, there was no statistically significant difference in the prevalence of EBV and HHV-8 DNA in the IPF specimens and controls in this study.
Molecular Pathology
Amir Hossein Jafarian; Melika Kooshki forooshani; Farzane Farzad; Nema Mohamadian Roshan
Abstract
Background & Objective: In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, ...
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Background & Objective: In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, differentiation, and migration of malignant cells. The objective was to evaluate the possible relation between FGFR1 over-expression and amplification in TNBCs and other clinicopathological variables. Methods: In this cross sectional study, purposive sampling was used to collect eighty-four TNBC specimens from mastectomy specimens collected between 2013 and 2017. Tissue microarrays were evaluated for FGFR1 over-expression and amplification respectively by immunohistochemistry (IHC) staining and real time Polymerase Chain Reaction (PCR). The needed clinical and paraclinical information were obtained from patients’ files. To analyze the correlation among prognostic factors, we used a wide range of different statistic methods, namely Chi-square test, independent t-test, Fisher's exact test, and ANOVA. Result: FGFR1 over-expression was found in 15 of the 84 samples (17.9%). FGFR1 gene amplification was observed in 33.3% (28 of 84) of the samples. We found no association between FGFR1 and clinicopathological parameters, including tumor grade, stage, and patient survival (P>0.005). Conclusion: FGFR1 over-expression and amplification may not be related to clinicopathological parameters, namely age, stage, and grade of the cancer not to mention TNBC survival. Using FGFR1 as a prognostic factor in TNBCs requires further study.
Molecular Pathology
Amir Hossein Jafarian; Nema Mohammadian Roshan; Masoumeh Gharib; Vahid Moshirahmadi; Aida Tasbandi; Amir Ali Ayatollahi; Hossein Ayatollahi
Abstract
Background and Objective: The primary goal of this study is to develop a rigorous understanding ofthe correlation between COX-2 expression and malignant melanoma prognostic factors. Material and Methods: In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related ...
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Background and Objective: The primary goal of this study is to develop a rigorous understanding ofthe correlation between COX-2 expression and malignant melanoma prognostic factors. Material and Methods: In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related stained slides were reviewed by two pathologists. The results were interpreted according to the COX2 staining index (SI), tumor thickness (Breslow, Clark), number of mitoses per 10 hpf, and melanoma types. Gender, lymph node involvement, metastasis, and survival were considered as evaluation factors as well. Results: The expression of the COX-2 protein was evident in 98.4% of cases. A strong Staining Index(SI) was reported in 60% of all melanomas, moderate staining was detected in 20.8% and weak staining in 10%; 1.6% of studied cases showed no staining. Benign nevus specimens showed no staining for the COX-2 enzyme. Conclusion: We have demonstrated that COX-2 is strongly expressed in the majority of malignant melanomas and that the SI score of COX-2 is related to the number of mitoses, tumor thickness (based on Clark level and Breslow), melanoma sub-type, lymph node involvement, and metastases; No association was noted between the anatomic site, gender, and survival. COX-2 can be applied as a prognostic factor in malignant melanoma and a promising candidate for future target therapies.
Molecular Pathology
Sahand Mohammadzadeh; Zahra Jowkar; Mitra Mirzaee; Bita Geramizadeh
Abstract
Background and Objective: Epidermal growth factor receptor (EGFR) gene mutation, especially in exons 18 to 21, is an important predictor of the response rate of lung adenocarcinoma to tyrosine kinase inhibitors. There are variable reports from Asian and European countries, as well as North America, about ...
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Background and Objective: Epidermal growth factor receptor (EGFR) gene mutation, especially in exons 18 to 21, is an important predictor of the response rate of lung adenocarcinoma to tyrosine kinase inhibitors. There are variable reports from Asian and European countries, as well as North America, about the frequency of the EGFR mutation in lung adenocarcinoma, yet molecular study about this incidence has been published from Iran. In this study, we investigated the frequency of this mutation in our center, which is the largest referral center in the south of country. This report will be the first published article about EGFR mutational analysis from Iran.Methods: During the study period (September 2011 till September 2016) i.e. 5 years, there have been 50 cases of pathologically-confirmed lung adenocarcinoma. These cases underwent mutational analysis for exons 18 to 21 of the EGFR gene by PCR and DNA sequencing. All demographic findings were also extracted from the patients’ charts and recorded.Results: There were 30 male and 20 female patients, with an average age of 58 years. The overall frequency of EGFR mutation was 28% (14 out of 50). The most common mutation was Del 19 (10 of 14, 71.4%), 3 mutations were found in exon 20 and one mutation was found in exon 21. EGFR mutations were more frequent in women than in men (30% versus 26.7%) and in nonsmokers than in smokers (37.9% versus 14.3%).Conclusion: Lung adenocarcinoma with EGFR mutation shows strong association with female non-smokers. Our results showed an intermediate frequency of this mutation, which was higher than results from Western countries and lower than most Asian countries.
Molecular Pathology
Geita Saadatnia; Aboutaleb Saremi; Behrouz Salehian; Pirooz Salehian
Abstract
Background and Objective: For nearly a century, it has been suspected that reproductive tract infections play an etiologic role in uterine leiomyoma. However, no epidemiologic study of leiomyoma has used the polymerase chain reaction (PCR) to compare uterine tissues from cases and non-cases, and to investigate ...
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Background and Objective: For nearly a century, it has been suspected that reproductive tract infections play an etiologic role in uterine leiomyoma. However, no epidemiologic study of leiomyoma has used the polymerase chain reaction (PCR) to compare uterine tissues from cases and non-cases, and to investigate associations between uterine leiomyoma and infections detected by PCR.Methods: In this case-control study, 92 leiomyoma tissues from cases, and 94 myometrial tissue from controls were screened by PCR for cytomegalovirus, Chlamydia trachomatis, herpes simplex virus-1, 2, and human papillomavirus typed as 16/18 or another strain. Multivariable analysis used age-adjusted logistic regression, and generalized linear regression as appropriate.Results: In the uterine tissues of cases and unmatched controls, the prevalence of infection was: cytomegalovirus (32.6%, 7.4%), C. trachomatis (23.9%, 37.2%), herpes simplex virus-1,2 (25.0%, 13.8%), human papillomavirus 16/18 (13.0%, 10.5%). Leiomyoma was associated with cytomegalovirus (Odds Ratio (O.R.) 6.10; 95% confidence interval (C.I.), 2.40, 15.55) and Chlamydia (O.R. 0.47; 95% C.I. 0.23, 0.97). Likewise, the log count of leiomyoma was higher with cytomegalovirus (+0.65, 95% C.I. +0.34, +0.95) and lower with Chlamydia (-0.71, 95% C.I. -1.12, -0.29).Conclusion: This first application of PCR to leiomyomata and control uterine tissues from non-cases reveals that cytomegalovirus is associated with the presence, number, and volume of uterine leiomyoma, while C. trachomatis is inversely associated with leiomyoma, but only in the absence of cytomegalovirus. Current findings provide preliminary evidence that common reproductive tract infections contribute to the growth and control of at least some cases of uterine leiomyoma.
Molecular Pathology
Navid Bazzaz; Nazila Nouraee Nouraee; Ali Zare-Mirzaie; Seyed Javad Mowla Mowla; Maryam Shahali; Mohammad Vasei
Volume 13, Issue 4 , October 2018, , Pages 422-428
Abstract
Background and Objective: Wilms’ tumor (WT) is the most common genitourinary tract tumor in children. MicroRNAs (miRNAs) are small non-coding RNAs; their role in the pathogenesis of many types of human cancers has been identified. We aimed to evaluate the expression of miR-21, a well-known oncomir, ...
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Background and Objective: Wilms’ tumor (WT) is the most common genitourinary tract tumor in children. MicroRNAs (miRNAs) are small non-coding RNAs; their role in the pathogenesis of many types of human cancers has been identified. We aimed to evaluate the expression of miR-21, a well-known oncomir, in WT tissue samples which is a very common urinary tract malignancy in children. Methods: We performed chromogenic in situ hybridization (CISH) to detect the sub-cellular localization of miR-21 in 25 formalin-fixed, paraffin-embedded (FFPE) samples of WT. We also evaluated miR-21 expression in 24 of these blocks and 6 normal kidneys as controls using quantitative real-time PCR technique. Results: While our real-time PCR analysis showed miR-21 significant overexpression in 4 tumors compared to the normal kidney samples, we could not detect significant ISH signal in any of these samples. Conclusion: Low expression of miR-21 in WT might pinpoint the weak involvement of this miRNA in the pathogenesis of this cancer.
Molecular Pathology
Freidoon Solhjoo; Akbar Safaie; Ahmad Monabati; Maral Mokhtari; Moeinadin Safavi
Volume 13, Issue 4 , October 2018, , Pages 438-446
Abstract
Background and Objective: Identification of cytogenetic and molecular changes plays an important role in acute myeloid leukemia (AML) patients. Thus, they are used in classification, prognosis and treatment of the disease. The CD123 expression and FLT3 gene mutations are also the variations that may ...
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Background and Objective: Identification of cytogenetic and molecular changes plays an important role in acute myeloid leukemia (AML) patients. Thus, they are used in classification, prognosis and treatment of the disease. The CD123 expression and FLT3 gene mutations are also the variations that may assist in prognosis and treatment of patients with AML.Methods: This study was performed on 76 patients as new cases of AML. The correlation between CD123 immunohistochemical (IHC) expression and FLT3 gene mutations with each other as well as morphological, immunophenotypical and cytogenetic factors was studied.Results: The results represented the CD123 IHC expression in 55.3% and FLT3 gene mutations in 28.9% of cases. We found that 81.3% of patients who had FLT3/ITD gene mutations revealed IHC of CD123 expression (P=0.019). The CD123 expression against FLT3 was also correlated with monocytic differentiation in bone marrow blasts (P=0.031). There were significant correlations between IHC expression of CD123 and FLT3/ITD mutations with a high percentage of aspirated bone marrow blasts (P=0.01 and P=0.006, respectively) as well as the lack of CD34 expression in bone marrow blasts (P=0.007 and P=0.021, respectively).Conclusion: The CD123 IHC positive AMLs were correlated with certain pathologic features, some of which can be similar with correlations of background mutation of FLT3/ITD; According to the negative predictive value (NPV), 88.2% of CD123 IHC showed FLT3 gene mutation. In addition to its use in targeted therapy, it could be a marker to decide what molecular tests to use in the next steps.
