Breast Pathology
Ramesh Omranipour; Newsha Nazarian; Sadaf Alipour; Alireza Abdollahi; Bita Eslami
Abstract
Background & Objective: Human epidermal growth receptor-2 (HER2) gene amplification is an important predictive and prognostic factor in breast cancer treatment. However, the expression of HER2 determined by immunohistochemistry (IHC) is considered as borderline in some cases, and confirmation of ...
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Background & Objective: Human epidermal growth receptor-2 (HER2) gene amplification is an important predictive and prognostic factor in breast cancer treatment. However, the expression of HER2 determined by immunohistochemistry (IHC) is considered as borderline in some cases, and confirmation of the HER2 status by either fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) is necessary for correct treatment decision-making. Considering the high cost of FISH and CISH, we aimed to investigate whether clinicopathological findings of the tumor could predict the HER2 status. Methods: A retrospective study was performed using the data from 584 patients with breast cancer with HER2-borderline disease, confirmed by IHC. Final HER2 status, pathologic tumor size and type, nodal involvement, Ki67 index, presence of estrogen and progesterone receptors (ER, PR), lymphovascular invasion (LVI), and stage were retrieved from the clinical records.Results: One hundred twenty-one (20.7%) patients were HER2-positive according to the FISH or CISH results. Logistic regression analysis showed that the pathologic size was positively associated with HER2 positivity with an odds ratio (OR) of 1.02 (95% CI: 1.01-1.04). In addition, the adjusted OR illustrated a statistically significant association between HER2 positivity and PR negativity (OR= 2.22, 95% CI: 1.29-3.83).Conclusion: In HER2 borderline breast cancer, HER2 positivity significantly increases with tumor size and PR negativity. Further studies are recommended that may find an applicable model to predict the actual status of HER2 in borderline cases.
Breast Pathology
KUMARGURU B N; RAMASWAMY A S; ARATHI C A; SWATHI D
Abstract
Background & Objective: Invasive breast carcinoma (IBC) is the most commonly diagnosed cancer among women in India. The conventional visual method of evaluation of Tumor-Stroma Ratio (TSR) and Stromal Tumor-Infiltrating Lymphocytes (sTIL) appears to be subjective. The present study aims to evaluate ...
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Background & Objective: Invasive breast carcinoma (IBC) is the most commonly diagnosed cancer among women in India. The conventional visual method of evaluation of Tumor-Stroma Ratio (TSR) and Stromal Tumor-Infiltrating Lymphocytes (sTIL) appears to be subjective. The present study aims to evaluate the utility of the indigenously designed square grid method for the evaluation of tumor-stroma ratio and stromal tumor-infiltrating lymphocytes in invasive breast carcinoma by assessing the inter-observer variability.
Methods: This was a retrospective study conducted at a rural tertiary care referral institute from July 2018 to June 2020. In each case, microphotographs were taken from 10 representative fields in H&E-stained sections for evaluating TSR in low-power and sTIL in high-power. Both the parameters were evaluated employing an indigenously designed square grid applied onto microphotographs in the power-point slides by making use of principles of the Pythagorean theorem. Both parameters were separately evaluated by two pathologists. Cohen kappa statistics was the statistical tool used to analyze inter-observer variability.
Results: Thirty cases were analyzed. Invasive breast carcinoma of no special type (IBC-NST) was the most common histopathological type (26 cases (86.67%)). For TRS evaluation, a Kappa value of 0.78 suggested substantial agreement with an agreement of 91.67%. For sTIL evaluation, a Kappa value of 0.51 suggested moderate agreement with an agreement of 88.33%. The P-values were statistically highly significant (P<0.001).
Conclusion: Square grid method is a novel technique for evaluating TSR and sTIL in invasive breast carcinoma. It can be considered an example of the application of Pythagoras’ theorem in Pathology.
Breast Pathology
Primariadewi Rustamadji; Elvan Wiyarta; Ineke Anggreani
Abstract
Background & Objective: Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) therapy need biomarkers to track their progress. Because of the relationship between NFkB, Survivin, and Cyclin D1 with NC resistance, the different expression levels of each of these biomarkers ...
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Background & Objective: Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) therapy need biomarkers to track their progress. Because of the relationship between NFkB, Survivin, and Cyclin D1 with NC resistance, the different expression levels of each of these biomarkers can be different between pre- and post-NC in IBC. However, no research has examined the correlation between these biomarkers before and after the NC expression. This study aimed to determine the correlation among them.Methods: Biomarkers expression (low and high) was used to classify 30 samples. ER, PR, HER2, Ki-67 status, tumor grade, age, and NC response were assessed. The amounts of Survivin, Cyclin D1, and NFkB were evaluated using immunohistochemistry, and samples were classified based on the cut-off. Chi-square and linear regression were used to evaluate the data.Results: No significant association was found with the changes in the expression of Survivin, Cyclin D1, and NFkB, both before and after the NC. Significant moderate correlations were shown between before and after the NC Survivin expression (r = 0.513) and Cyclin D1 expression (r = 0.543). The correlation between expression of NFkB before and after the NC was not significant.Conclusion: The high potential of these proteins as prognostic indicators was demonstrated by the strong positive association between the expression of Survivin and Cyclin D1 before and after the NC. This upregulation of biomarkers indicates chemoresistance in developing IBC in the presence of NC.
Breast Pathology
Faeze Shirian; Parvin Kheradmand; Nastaran Ranjbari; Hodjatollah Shahbazian; Seyed Mahmoud Latifi
Abstract
Background & Objective: During the last decade, biological markers of breast cancer have been considered to predict the degree of histology, behavior, and extent of tumor invasion and the possibility of lymph node involvement. The aim of this study was to evaluate the expression of GCDFP-15 in different ...
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Background & Objective: During the last decade, biological markers of breast cancer have been considered to predict the degree of histology, behavior, and extent of tumor invasion and the possibility of lymph node involvement. The aim of this study was to evaluate the expression of GCDFP-15 in different grades of invasive ductal carcinoma, as the most common type of breast cancer.Methods: In this retrospective study, paraffin blocks of tumors of 60 breast cancer patients registered in the histopathology laboratory of Imam Khomeini Hospital in Ahvaz between 2019 and 2020 were reviewed. Information on grade, invasion, stage and lymph node involvement was extracted from the pathology reports and immunohistochemical staining for GCDFP-15 was performed. Data were analyzed by SPSS 22.Results: GCDFP-15 marker expression was observed in 20 out of 60 breast cancer patients (33.3%). GCDFP-15 staining intensity was weak in 7 cases (35%), moderate in 8 cases (40%), and strong in 5 cases (25%). The patient's age and sex showed no significant relationship with the expression of GCDFP-15 and intensity of staining. Expression of the GCDFP-15 marker was correlated significantly with tumor grade, stage, and vascular invasion (P<0.05)) and its expression was higher in tumors with a lower grade, less depth of invasion, and no vascular invasion but unrelated to perineural invasion, lymph node involvement, and tumor size. The intensity of staining for GCDFP-15 showed significant relationship with the tumor grade (P<0.0001) but unrelated to the other factors.Conclusion: GCDFP-15 marker may be significantly associated with tumor grade, depth of invasion, and vascular invasion, thus can be used as a prognostic marker.
Breast Pathology
Aida Alizamir; Sakineh Dehghan Azad; Azar Pirdehghan; Arash Moradi
Abstract
Background & Objective: Female breast cancer is one of the most prevalent malignancies among women. The critical step in managing breast cancer is to diagnose it accurately. Hence, peripheral blood-based tests are one of the most favorable and less invasive methods to study. Recent studies investigated ...
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Background & Objective: Female breast cancer is one of the most prevalent malignancies among women. The critical step in managing breast cancer is to diagnose it accurately. Hence, peripheral blood-based tests are one of the most favorable and less invasive methods to study. Recent studies investigated and evaluated the inflammation parameters such as neutrophil: lymphocyte ratio (NLR), the platelet: lymphocyte ratio (PLR), and the C-reactive protein (CRP) levels. The elevation in mentioned parameters was proposed as a key factor in cancer progression. The main goal of this study was to investigate the association of NLR, PLR, and CRP levels in patients with breast lesions.Methods: The NLR, PLR, and CRP levels were calculated from 200 female patients with either benign or malignant lesions.Results: The cut-off values of NLR, PLR, and CRP were 1.24, 96, and 10.36 mg/L, respectively. A significant difference in NLR (P<0.001), PLR (P<0.001), and CRP levels (P<0.001) were observed between the two major studied cohorts.Conclusion: Elevated NLR, PLR, and CRP levels could predict the presence of malignancy. In addition to the low cost and properties of the mentioned methods, utilization of this data could facilitate and improve clinical decision-making for treatment.
Breast Pathology
Sajitha K; Meenakshi Arumugam; Jayaprakash Shetty; Reshma A Shetty; Ritu Asnani; Prashanth Shetty
Abstract
Background & Objective: Breast cancer is the most common cancer in developed and developing countries. This study mainly addresses the issue of an equivocal result in IHC, which then needs further assessment if the patient has to receive targeted therapy. The study aimed to detect the expression ...
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Background & Objective: Breast cancer is the most common cancer in developed and developing countries. This study mainly addresses the issue of an equivocal result in IHC, which then needs further assessment if the patient has to receive targeted therapy. The study aimed to detect the expression of Her2/neu protein in breast cancer by immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) and evaluate concordance and discordance between the two methods. Also, the clinicopathological parameters in these patients were studied in association with ER, PR, HER-2, and Ki-67.Methods: This study was conducted on 34 female carcinoma breast specimens, including core biopsies and mastectomies. Each case underwent histopathological and immunohistochemical studies for (Estrogen Receptor) ER, (Progesterone Receptor) PR, (Human Epidermal growth factor Receptor 2) HER-2, and Ki-67. In addition, FISH was done on all the samples to detect Her2 gene amplification.Results: The overall concordance between the two tests was 79.41% while the concordance between the two tests in equivocal cases, was 14.3%. ER/PR expression and HER-2 amplification were inversely associated. Also, Ki-67 expression was not associated with the side size of the lesion, lymphovascular invasion, and lymph node metastasis. Age less than 50 at presentation and infiltrating ductal carcinoma histological type showed increased proliferation index.Conclusion: The highest concordance between FISH and IHC was noted in IHC positive and negative cases, whereas IHC equivocal cases showed low concordance. FISH accurately determines the assessment of HER2 expressions in equivocal cases.
Breast Pathology
Primariadewi Rustamadji; Elvan Wiyarta; Kristina Anna Bethania
Abstract
Background & Objective: Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer, which mainly causes axillary lymph-node metastasis (ALNM). Building on our previous research, we wanted to explore the optimal combination of AKT2, CD44v6, and MT1-MMP for the ...
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Background & Objective: Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer, which mainly causes axillary lymph-node metastasis (ALNM). Building on our previous research, we wanted to explore the optimal combination of AKT2, CD44v6, and MT1-MMP for the ALNM prediction.Methods: The presence or absence of ALNM was used to separate 46 paraffin blocks containing IBC-NST primary tumors into two groups. Age, tumor grade, tumor size, receptor status (ER, PR, HER2, Ki-67, TOP2A), and test biomarker expression were evaluated. Biomarker expressions were assessed by IHC staining and categorized according to their respective cut-offs from our previous study, while other data were collected from archives. Data was gathered and analyzed using univariate, multivariate, and AUROC models.Results: The expression of CD44v6 (OR: 12.77, 95% CI: 2.18-87.12, P=0.005) was identified as the independent variable for ALNM. Meanwhile, AKT2 expression (OR: 3.22, 95% CI: 0.36-22.41, P=0.237) and MT1-MMP expression (OR: 5.35, 95% CI: 0.83-34.54, P=0.078) did not demonstrate a statistically significant independent association in respect to ALNM. Combining AKT2 and MT1-MMP on CD44v6 increased overall accuracy by 4% compared to CD44v6 alone (AUROC 0.89 vs. 0.85).Conclusion: The combined usage of AKT2, CD44v6, and MT1-MMP revealed no significant change compared to CD44v6 alone. Due to cost and practicality, we propose using CD44v6 as a biomarker predictor of ALNM in IBC-NST.
Breast Pathology
Amin Jafari Oliayi; Shahriar Dabiri
Abstract
Background & Objective: Long noncoding RNAs (lncRNAs) as challenging molecules are more known compared to those in the last decade. These transcripts have been validated for carcinogenesis in many types of tissue. Functions of lncRNAs in cancer induction include cell cycle, epithelial to mesenchymal ...
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Background & Objective: Long noncoding RNAs (lncRNAs) as challenging molecules are more known compared to those in the last decade. These transcripts have been validated for carcinogenesis in many types of tissue. Functions of lncRNAs in cancer induction include cell cycle, epithelial to mesenchymal transition progression, apoptosis inhibition, cell migration, and invasion stimulation . LncRNA small nucleolar host (SNHG6) have been proven as an oncogenic transcript in many types of cancer.Methods: RNA extraction was performed for 47 breast specimens in patients with cancer and cDNAs were synthesized. Relative expression of target variants was determined by qPCR and calculated based on the ΔΔCt method. SNHG6 203 was cloned into pcDNA 3.1+ vector for overexpression in MCF7 (HER2-) and SK-BR3 (HER2+) cells. The cell cycle progression of transfected cells was assessed by flow cytometry. Cell migration ability of transfected cells was evaluated by the scratch method and Image J software. Finally, cell viability was assessed by the MTT method.Results: Among four splice variants of SNHG6 (202, 203, 204, and 207), SNHG6 203 was proved as an overexpressed splice variant in breast cancer tumors. This transcript was expressed in HER2-negative breast tumors more frequently than in the positive ones. Overexpression of this variant in target cells resulted in cell cycle progression of MCF7 as HER2-negative cells. Moreover, the overexpression of SNHG6 203 led to a lower migration ability of MCF7 cells and a non-significant reduction of their viability as HER2-negative breast cancer cells.
Breast Pathology
Geetha V Patil Okaly1; Akshatha C; Sandhya N; Akina Prakash; M N Suma; Ashwini Nargund; Shankar Anand; C Ramachandra; Libin Babu Cherian
Abstract
Background & Objective: Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling ...
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Background & Objective: Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma.Methods: The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute.Results: A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively.Conclusion: Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to the diagnosis of the process.
Breast Pathology
Rashim Sharma; Poonam Abhay Elhence; Meenakshi Rao; Sudeep Khera; Deepak Vedant; Ramkaran Chaudhary; Puneet Pareek; Jeewan Ram Vishnoi; Sanjeev Misra
Abstract
Background & Objective: Breast cancer is the leading cancer among Indian women and accounts for about 25% of all cancer cases worldwide. The present study aimed to assess Programmed Death Ligand-1 (PD-L1) expression in tumoral cells and tumor-infiltrating lymphocytes (TILs) and evaluate their correlations ...
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Background & Objective: Breast cancer is the leading cancer among Indian women and accounts for about 25% of all cancer cases worldwide. The present study aimed to assess Programmed Death Ligand-1 (PD-L1) expression in tumoral cells and tumor-infiltrating lymphocytes (TILs) and evaluate their correlations with the Ki-67 labelling index in invasive breast carcinomas (IBC).Methods: This descriptive observational study was conducted during 2016-2018 and included all diagnosed cases of IBC. The relationships between PD-L1 expression, TILs, hormone receptors, Ki-67, and clinicopathological parameters were studied in IBC. Statistical analysis was performed by SPSS version 23.Results: Out of 114 evaluated cases, 33.33% (N=38) showed PD-L1+ expression in tumor cells and 47.37% (N=54) had PD-L1+ expression in TILs. A high Ki-67 index was observed in 96 cases. Moreover, 49 patients were estrogen receptor (ER)- and 65 were ER+. We observed that 22 of 49 ER- and 49 of 65 ER+ subjects showed PD-L1+ expression, respectively.Conclusion: Our results showed a significant relationship between PD-L1 expression in tumoral cells and TILs, as well as between Ki-67 and TILs. In addition, an inverse correlation was noted between PD-L1 expression and ER. The PD-L1 expression in tumors and TILs and correlation with high Ki-67 may prove the importance of PD-L1 in targeted chemotherapy. An inverse relationship between PD-L1 and ER expression in tumoral cells suggests scope for immunotherapy in ER- IBC. However, further research with more cases is required.
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.
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.
Breast Pathology
Javad Charostad; Mohsen Nakhaie; Azarakhsh Azaran; Gholam Abbas Kaydani; Akram Astani; Azim Motamedfar; Manoochehr Makvandi
Abstract
Background & Objective: The role of Epstein-Barr Virus in development of breast cancer is frequently studied. In this regard, miRNAs are among the contributing elements in the molecular pathophysiology of EBV-related diseases. In addition, a growing number of host miRNAs are believed to be implicated ...
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Background & Objective: The role of Epstein-Barr Virus in development of breast cancer is frequently studied. In this regard, miRNAs are among the contributing elements in the molecular pathophysiology of EBV-related diseases. In addition, a growing number of host miRNAs are believed to be implicated in pathogenesis of breast cancer. MiR-218 is a tumor suppressive miRNA that is subjected to dysregulation in various EBV-associated cancers. We aimed to investigate the frequency of EBV and its relationship with expression status of tumor suppressive miR-218 in breast cancer and adjacent normal tissue.Methods: A total number of 51 fresh malignant breast cancer tissues (cases) and their adjacent normal tissues (controls) were collected. Nested-PCR and RT-qPCR were set to identify EBV frequency and miR-218 expression in cases and controls, respectively.Results: Out of all samples, 6.8% (7/102) comprising 11.6% (6/51) in malignant tissues and 1.9% (1/51) in normal control tissues were positive for EBV (P<0.05). Quantitative data showed that miR-218 was significantly downregulated in malignant tissues compared to control tissues (P<0.0001). In addition, reduced expression of miR-218 was associated with adverse clinical outcomes, metastasis, and higher grades of malignancy. Given the presence of EBV, lower expression of miR-218 was observed in breast cancer group in comparison with normal group (P<0.05). Conclusion: Our results raise the possibility of the relation between EBV infection and miR-218 downregulation in breast cancer and propose further investigations in this regard.
Breast Pathology
Sujata Mallick; Mahasweta Mallik; Rabindra Nath Chatterjee; Puskar Shyam Chowdhury
Abstract
Background & Objective: Liver lesions are difficult to diagnose and to differentiate primary from metastatic carcinoma, while Biopsy has its limitations. Cell block technology is easily accessible with high diagnostic accuracy. Our aim is 1) To find the role of cell block technology as an alternative ...
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Background & Objective: Liver lesions are difficult to diagnose and to differentiate primary from metastatic carcinoma, while Biopsy has its limitations. Cell block technology is easily accessible with high diagnostic accuracy. Our aim is 1) To find the role of cell block technology as an alternative to biopsy in identifying liver lesions; 2) To find the efficacy of cell block along with immunohistochemistry (IHC) and ancillary studies in differentiating primary from metastatic lesions; 3) To identify the site of origin of metastatic lesions. This is a descriptive study undertaken in two tertiary care hospitals over a period of three years.Methods: Retrospective review of adequate samples from fine needle aspirations from liver lesions under radiological coverage, converted into cell block was done. IHC was applied as needed. Usefulness of cell block preparation was evaluated, and the final diagnosis correlated with the biopsy results.Results: Analysis of 323 cases found sensitivity of 98.75% and positive predictive value of 99% for all lesions. Sensitivity for metastatic carcinomas was slightly more than hepatocellular carcinoma. However, accuracy of cell block results for individual metastatic lesions and site of origin was less. IHC and morphological pattern worked as an important adjunct in the final diagnosis. On the other hand, contribution of viral markers as a supplement in the final work up was ambiguous. Conclusion: High precision of validity results of cell block technology in comparison with biopsy highlights its pivotal role in conjunction with supportive tests for diagnosing and differentiating liver lesions as well as identifying primary sites in liver metastasis.
Breast Pathology
Hiva Saffar; Dorna Motevalli; Nasibeh Seirfar; Mahsa Ebrahimi; Perikala Vijayananda Kumar; Farid Kosari; Hedieh Moradi Tabriz; Sadaf Naderi; Golsa Shekarkhar
Abstract
Myofibroblastoma (MFB) of the breast is an uncommon entity of benign spindle neoplasms of the breast. This tumour possesses a broad spectrum of histomorphological patterns. Distinguishing of myofibroblastoma variants from malignant mimics of this benign neoplasm is essential for pathologists to avoid ...
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Myofibroblastoma (MFB) of the breast is an uncommon entity of benign spindle neoplasms of the breast. This tumour possesses a broad spectrum of histomorphological patterns. Distinguishing of myofibroblastoma variants from malignant mimics of this benign neoplasm is essential for pathologists to avoid further invasive surgical procedures. In this article, we report the clinical, morphological, and immunohistochemical features of three cases, including two females and one male patient with mammary myofibroblastoma with emphasis on the histomorphological findings. As there is not yet enough information about MFB, more reports of MFB are still required to more clarify the pathogenesis and potential predisposing factors of this rare type of breast tumours.
Breast Pathology
Nazanin Mirmohseni Namini; Alireza Abdollahi; Monireh Movahedi; Amirnader Emami Razavi; Reza Saghiri
Abstract
Background & Objective: This study examined the potential of human epididymis protein 4 (HE4) as a marker in early diagnosis or as a prognostic factor for breast cancer (BC) patients.Methods: A total of 31 patients diagnosed with BC were enrolled in the study between 2008 and 2018. The mRNA and protein ...
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Background & Objective: This study examined the potential of human epididymis protein 4 (HE4) as a marker in early diagnosis or as a prognostic factor for breast cancer (BC) patients.Methods: A total of 31 patients diagnosed with BC were enrolled in the study between 2008 and 2018. The mRNA and protein expression levels of HE4 were analyzed by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) in the BC tissue and the non-tumoral adjacent tissue. Using ELISA technique, HE4 plasma levels were also measured in 43 BC patients compared to 43 healthy individuals. The correlation between HE4 expression and clinicopathological features was then investigated.Results: An increase in HE4 expression was observed at mRNA and protein levels in the BC group compared to the control group (p <0.01, p <0.0001, respectively). In addition, the relative expression of HE4 mRNA in BC patients showed a significant correlation with the differentiation grade of cancer cells (p <0.001). Plasma levels of HE4 was also associated with grade (p <0.0001), stage, and tumor size in BC patients (for both p <0.01). Patients with metastatic BC (p <0.01), lymphatic invasion, and lymph node involvement (for both p <0.05) showed significantly higher plasma levels of HE4 expression than patients without metastasis.Conclusion: According to our findings, upregulation of HE4 is probably related to invasive BC phenotype, and measuring plasma levels of HE4 could be useful as a screening test in early diagnosis of BC.
Breast Pathology
Zeinab Vosough; Shima Golbini; Majid Sharbatdaran; Akramossadat Hosseini
Abstract
Background & Objective: Breast cancer is the most common malignancy in Iranian women and worldwide. Lymphatic vessel invasion (LVI) was found to be an independent prognostic factor in many carcinomas, including invasive carcinoma of the breast. The aim of this study was to compare the hematoxylin ...
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Background & Objective: Breast cancer is the most common malignancy in Iranian women and worldwide. Lymphatic vessel invasion (LVI) was found to be an independent prognostic factor in many carcinomas, including invasive carcinoma of the breast. The aim of this study was to compare the hematoxylin and eosin (H&E) staining method and the use of the immunohistochemistry (IHC) marker, D2-40, for evaluating LVI in breast carcinoma specimens. Materials & Methods: The study was conducted on 50 patients undergone surgery between the years 2010 and 2015 in Rohani Hospital, Babol, Iran with invasive carcinoma of the breast with Census sampling method. LVI was assessed using H&E staining and two IHC markers, i.e., D2-40 and CD31, by two surgical pathologists. Results: LVI was detected in 25 (50%) patients by H&E and in 14 (28%) patients by D2-40. Twelve out of 25 patients with positive LVI in H&E were confirmed by D2-40 and 2 out of 25 patients with negative lymphatic vessel in H&E. Only one case showed weak staining of CD31 proving LVI. These results showed a significant difference between the H&E staining and D2-40 IHC study for LVI detection (p =0.004). Conclusion: The D2-40 IHC marker is helpful in the diagnosis and confirmation of LVI in invasive carcinoma of the breast. CD31 is not suitable for the evaluation of lymphatic vessels.
Breast Pathology
Armin Borhan; Zohreh Nozarian; Alireza Abdollahi; Reza Shahsiah; Hadiseh Mohammadpour; Arash Borhan
Abstract
Background & Objective: Nowadays, actin-binding proteins such as Villin and Gelsolin have been considered to be associated with aggressive tumors. This study mainly aims to determine the relationship between Gelsolin and Villin genes expression and metastasis of axillary lymph nodes in patients with ...
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Background & Objective: Nowadays, actin-binding proteins such as Villin and Gelsolin have been considered to be associated with aggressive tumors. This study mainly aims to determine the relationship between Gelsolin and Villin genes expression and metastasis of axillary lymph nodes in patients with breast cancer.Methods: The included population consisted of 40 confirmed cases of female breast cancer (including 20 patients with breast cancer along with axillary lymph node metastasis and 20 patients without axillary lymph node metastasis). Expression of Villin and Gelsolin genes was evaluated using Real-time PCR and pre-designed primers.Results: The mean expression level of Villin in groups with and without axillary lymph node metastasis was 3.33±1.35 and 0.87±0.88, respectively (p <0.001). The mean Gelsolin expression levels in both groups (with and without axillary lymph node metastasis) were 4.13±2.40 and 1.00±0.35, respectively (p <0.001). The significant relationships were independent of individuals’ age.Conclusion: Patients with axillary lymph node metastasis may express significant higher level of Villin and Gelsolin gens.
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.
Breast Pathology
Danial Fazilat-Panah; Somaye Vakili Ahrari Roudi; Alireza Keramati; Azar Fanipakdel; Mohammad hadi Sadeghian; Fatemeh Homaei Shandiz; Soudabeh ShahidSales; Seyed Alireza Javadinia
Abstract
Background & Objective: Prediction of response to neoadjuvant treatment is an important part of treatment of patients with breast cancer. This study aimed to assess changes in serum levels of Cytokeratin 18 during neoadjuvant chemotherapy in patients with locally advanced breast cancer and its association ...
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Background & Objective: Prediction of response to neoadjuvant treatment is an important part of treatment of patients with breast cancer. This study aimed to assess changes in serum levels of Cytokeratin 18 during neoadjuvant chemotherapy in patients with locally advanced breast cancer and its association with neoadjuvant treatments. Methods: This research was performed on newly diagnosed breast cancer patients referred to Omid Radiotherapy Center and radiotherapy and oncology departments of Emam Reza and Ghaem hospitals, in Mashhad, Iran. Serum levels of M30 and M65 fragments of Cytokeratin 18 were measured before and 24 hours after the first course of neoadjuvant chemotherapy. Changes in serum levels of Cytokeratin 18 and its fragments and their correlation with pathologic response were analyzed. Result: Pre- and post-chemotherapy levels of M30 were respectively 223.9±18.94 and 250.7±23.92 U/L (P=0.24). For M65, these levels were respectively 301.5±313.9 and 330.2±352.2 U/L (P=0.1). Changes in M30 level during chemotherapy in patients with and without pathologic complete response were -20±92.69 and 43.1±106.5, respectively (P=0.1). For M65, these changes were respectively -247±55 and 76±240 (P=0.1). Baseline levels of M30 and M65 had no relation with menopausal status, tumor grade, hormone receptor status, Ki67 expression, molecular subtype, and stage. Conclusion: Our findings showed statistically insignificant changes in the level of Caspase-cleaved- (M30) and uncleaved- (M65) cytokeratin 18 fragments (apoptotic and necrotic indicators, respectively) during neoadjuvant chemotherapy in patients with breast cancer. There was no notable relationship between tumor-related factors and either baseline levels or serum changes of CK18 fragments. Also, there was no correlation between M30/M65 level and pathologic response to neoadjuvant chemotherapy.
Breast Pathology
Maryam Kadivar; Fatemeh Aram
Abstract
Background & Objective:Ki-67 evaluation is an essential tool to define luminal A and B breast cancers, which is not yet systematized. The International Ki67 in Breast Cancer Working Group suggests the counting of 500 or 1000 cancer cells, which is a time-consuming process. Therefore, novel methods, ...
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Background & Objective:Ki-67 evaluation is an essential tool to define luminal A and B breast cancers, which is not yet systematized. The International Ki67 in Breast Cancer Working Group suggests the counting of 500 or 1000 cancer cells, which is a time-consuming process. Therefore, novel methods, such as the Eye-10 method and stepwise counting strategy, are proposed to facilitate measurement. Methods:Immunohistochemical staining of Ki67 was performed on 100 hormone-receptor-positive invasive ductal carcinoma specimens. Ki67LI was evaluated for each case, and then results were dichotomized by a cut-off point of 20%. Next, for each sample, an expert pathologist visually assessed percentages of Ki67-positive cells in 10% intervals at a glance (Eye-10 method). Finally, by using a dynamic process with rejection regions, Ki67 was defined so if the estimate belonged to the upper or lower rejection region, the Ki67 status had been determined and if the rejection region could not be reached after counting the maximum number of 400 tumor cells, the specimen was regarded as equivocal (stepwise counting strategy).Results:The comparison between Eye-10 and Ki67LI revealed almost perfect agreement (kappa coefficient =0.889), and the concordance between the stepwise counting strategy and Ki67LI was substantial (kappa coefficient =0.639).Conclusion:Both two methods left some results in the gray/intermediate zone, which is unavoidable. Both methods are much faster and simpler than evaluation of Ki67LI and are also reliable. Regarding the gray zone in both methods, further improvements in the methodology, as well as more analytical studies, are needed.
Breast Pathology
Alireza Abdollahi; Sepideh Jahanian; Nima Hemmati; Hadiseh Mohammadpour
Abstract
Background & Objective: Recent studies from gene profiling have revealed some genes that are overexpressed in the epithelial-mesenchymal transition (EMT) process and are responsible for its initiation and activation resulting in tumor progression and metastasis. The present study aimed to assess ...
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Background & Objective: Recent studies from gene profiling have revealed some genes that are overexpressed in the epithelial-mesenchymal transition (EMT) process and are responsible for its initiation and activation resulting in tumor progression and metastasis. The present study aimed to assess the role of genes involved in the EMT process and the association of these genes with axillary lymph node and vascular invasion in breast cancer (BC) patients. Methods: In this case-control study, the tumor samples were initially extracted from 33 BC patients. The samples of 15 BC tissues without vascular and axillary invasion were also prepared from the biobank as a control group. RNAs from both tumor and control samples were extracted and stabilized. For assessing overexpression in tumor tissues of selected 18 genes, the real time technique was employed. Results: There was a significant increase in MMP-2 gene fold expression in tumor cells with vascular invasion regardless of axillary involvement compared to the control group (P=0.0008) and also in the comparison of the control group with those with vascular invasion and not axillary lymph node involvement (P=0.003). In addition, gene fold expression of tissue inhibitors of metalloproteinase-1(TIMP-1) was decreased in axillary involving tumor cells compared to control group (P=0.045), and also in comparison with all samples that did not present any axillary lymph node involvements including the control group and the group with isolated vascular invasion (P=0.012). Conclusion: Overexpression of MMP-2 and under-expression of TIMP-1 were associated with more invasive behavior in breast tumor cells.
Breast Pathology
Amir Hosein Jafarian; Melika Kooshkiforooshani; Abdolshakor Rasoliostadi; Nema Mohamadian Roshan
Abstract
Background & Objective: In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression ...
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Background & Objective: In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors. Methods: In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented. Results: The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; P<0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; P=0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; P<0.001), and positive HER-2 (100% vs. 31.1%; P<0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression. Conclusion: The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.
Breast Pathology
Akbar Safaei; Ahmad Monabati; Maral Mokhtari; Mehdi Montazer
Abstract
The most widely used guideline for the breast cancer biomarker assessment and reporting (the 2013 ASCO/CAP guideline) does not state the unusual occurrence of cytoplasmic Her2/neu staining (1, 2).
We recently encountered a T2N1Mx ductal adeno-carcinoma which consisted of two dissimilar tumor cell populations. ...
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The most widely used guideline for the breast cancer biomarker assessment and reporting (the 2013 ASCO/CAP guideline) does not state the unusual occurrence of cytoplasmic Her2/neu staining (1, 2).
We recently encountered a T2N1Mx ductal adeno-carcinoma which consisted of two dissimilar tumor cell populations. The more prominent population (75% of tumor cells) was made up of sheets of neuroendocrine-like cells (NEL) and the other tumor cell population had a usual adenocarcinomatous histomorphology (UAC) (Fig. 1A). The NEL was ER+ (clone 073), PgR-(clone 636), 40% ki67 with distinct dot-like cytoplasmic Her2 staining (clone CB11) which is considered as negative regarding the current guidelines. The UAC was ER+, PgR+, 20% ki67, and Her2 negative (Fig. 1A-C). Moreover, NEL did not react with either chromogranin or synaptophysin, but it expressed neuron-specific enolase (NSE). Dual color Her2/neu chromogenic in situ hybridization probes (chromogenic ISH) established that both components were not amplified for this oncoprotein gene (Fig. 1D).
