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
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
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.
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.
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
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.
Samaneh Khorrami; Masoumeh Tavakoli; Elahe Safari
Abstract
Background and Objective: S100A8/A9 is a heterodimer calcium-binding protein which is involved in tumor cell proliferation, adhesion and invasion, and is proposed as a biomarker for better diagnosis and prognosis in many cancers. The aim of this study was to evaluate the simultaneous serum-based level ...
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Background and Objective: S100A8/A9 is a heterodimer calcium-binding protein which is involved in tumor cell proliferation, adhesion and invasion, and is proposed as a biomarker for better diagnosis and prognosis in many cancers. The aim of this study was to evaluate the simultaneous serum-based level of S100A8/A9 and CA15-3 as well-illustrated cancer biomarkers, as well as their prognostic value in breast cancer patients and healthy matched controls. Material and Methods: Thirty breast cancer patients at different stages of disease and healthy matched controls with no history of inflammatory, autoimmune diseases, or cancer, were enrolled in the study. The levels of S100A8/A9 and CA15-3 were assessed serologically using the Enzyme-linked immunosorbent assay (ELISA) method, and the relevance of these markers with patients’ clinicopathological features were subsequently assessed. Results: Based on our data, the serum levels of both S100A8/A9 and CA15-3 were significantly higher in patients compared to the healthy controls, and thus positively correlated with tumor size. Also, statistical analysis shows that the serum level of S100A8/A9 has 100% specificity and sensitivity (AUC = 1.00, 95% CI) for the diagnosis of breast cancer patients. Conclusion: According to our data as well as other observations, the S100A8/A9 heterodimer can be considered as a potential biomarker for the proper diagnosis and prognosis of breast cancer.
Biology & Genetic
Shadi Hosseini; Farkhondeh Behjati; Maryam Rahimi; Nazanin Taheri; Hamid Reza Khorram Khorshid; Fatemehte Aghakhani Moghaddam; Saghar Ghasemi Frouzabadi; Masoud Karimlou; Fereidoon Sirati; Elahe Keyhani
Volume 13, Issue 4 , October 2018, , Pages 447-453
Abstract
Background and Objective: The PI3K/AKT/mTOR pathway is known to play an important role in regulating angiogenesis both in normal and breast cancer (BC) tissues. PIK3CA amplification was reported in various malignancies, including approximately 10% of BC cases. The aim of this study was to identify the ...
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Background and Objective: The PI3K/AKT/mTOR pathway is known to play an important role in regulating angiogenesis both in normal and breast cancer (BC) tissues. PIK3CA amplification was reported in various malignancies, including approximately 10% of BC cases. The aim of this study was to identify the frequency of PIK3CA amplification in Iranian female patients suffering from BC. Additionally, possible association between PIK3CA amplification and P110α expression with microvascular density (MVD) was examined.Methods: DNA samples were extracted from paraffin embedded tumor tissue blocks and copy number changes were evaluated by MLPA Technique. The results were analyzed by coffalyzer software. The tissue expression of P110α and CD34 was assessed using immunohistochemistry.Results: Ten out of 40 samples (17.5%) showed amplification in PIK3CA gene and 22 out of 40 samples (55%) showed overexpression in P110α. For CD34, from 40 samples, 20 (50%), 15 (37.5%) and 5 (12.5%) had scores 1+, 2+ and 3+, respectively.Conclusion: No significant association was detected between gain of PIK3CA copy number and P110α or CD34 tissue expression.
Hossein Javid; Isaac Hashemy; Soudabeh Shahid sales; Nema Mohammadian Roshan; Tayyebeh Kianoosh; Farnaz Zahedi Avval
Abstract
Background & objective: Globally, breast cancer is the most common malignancy among females. Prohibition (PHB)-I, a homologous protein, was initially introduced as a suppressor gene for amplification process. Further, the protein has a key role in the cell cycle and is capable of inhibiting ...
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Background & objective: Globally, breast cancer is the most common malignancy among females. Prohibition (PHB)-I, a homologous protein, was initially introduced as a suppressor gene for amplification process. Further, the protein has a key role in the cell cycle and is capable of inhibiting DNA transcription in many cell types. Therefore, its possible role in different types of human malignancies is of interest. The current study aimed at examining the relationship between the tissue distribution of PHB-I and prognostic factors of breast cancer. Method: Paraffin-embedded tissue specimens of 33 patients diagnosed with breast cancer at Omid teaching Hospital, Mashhad, Iran were studied and a commercial monoclonal antibody was used to perform immunohistochemistry (IHC). The relationship between PHB-I tissue expression with age, disease stage, tumor grade and size, as well as hormone receptor status including estrogen (ER) and progesterone (PR) receptors, and Her-2 receptor were evaluated. Results: The Immunohistochemical analysis showed a relative increase in PHB-I tissue expression along with higher tumor grade (P=0.057). In addition, higher expression of ER and PR were observed (P=0.027 and 0.009, respectively). The age of patients and other prognostic factors including Her-2 receptor status and disease stage did not statistically correlate with PHB-I expression. Conclusion: An increased expression of PHB-I was observed in the breast cancer tumors of the current study patients compared with the anatomically healthy margin. Its coloration with some prognostic factors such as disease grade and expression of ER and PR might indicate the PHB-I potential application for diagnostic and patient management purposes.
Hematopathology
Vahid Moazed; Elham Jafari; Behjat Kalantari khandani; Ali Nemati; seyedamir benrazavi
Abstract
Background and objective:Breast cancer is the most common malignancy among women. The Neoadjuvant chemotherapy is the treatment of choice for non-operable tumors. The Ki67 is a proliferation marker that can be used to predict the therapeutic response to chemotherapy and the patients' prognosis. Methods: ...
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Background and objective:Breast cancer is the most common malignancy among women. The Neoadjuvant chemotherapy is the treatment of choice for non-operable tumors. The Ki67 is a proliferation marker that can be used to predict the therapeutic response to chemotherapy and the patients' prognosis. Methods: This retrospective study was carried out on 55 consecutive patients with breast cancer referred to a Training Tertiary Healthcare Center in Kerman, Iran since 2009 to 2014. After diagnostic approval, the tissue samples of patients were examined for estrogen and progesterone receptors, ki67 and HER2-neu markers by using immunohistochemical staining. Then the patients were treated with 6 cycles of Neoadjuvant chemotherapy regimens by Doxorubicin and Taxans or 4 chemotherapy cycles, containing Anthracycline and Cyclophosphamide and 4 cycles of Paclitaxel. After mastectomy, their samples were reexamined for ki67 again and classified into three groups (low: ki67<15%), medium (Ki67 = 16-30%) and high (Ki67> 30%). Results: Before chemotherapy, 54.5% of the patients had high expression of Ki67. But after chemotherapy, 52.7 of the patients had complete therapeutic response showing that the Ki67 level was reduced significantly (P=0.003). Conclusion: Before and after Neoadjuvant chemotherapy, Ki67 measurements may be used as a predictive marker of therapeutic response.
Fereshteh Ensani; Ramesh Omranipour; Isa Jahanzad; Azadeh Jafari; Shima Nafarzadeh; Pouyan Aminishakib
Abstract
Background &Objectives: Evaluation of estrogen receptor (ER), progesterone receptor (PR), and (human epidermal growth factor receptor-2) Her-2 on core needle biopsies (CNBs) is increasingly in use to diagnosis early breast cancer, but its concordance with surgical excision (SE) is not well documented. ...
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Background &Objectives: Evaluation of estrogen receptor (ER), progesterone receptor (PR), and (human epidermal growth factor receptor-2) Her-2 on core needle biopsies (CNBs) is increasingly in use to diagnosis early breast cancer, but its concordance with surgical excision (SE) is not well documented. Methods: The study included 100 formalin fixed, paraffin-embedded specimens of invasive breast carcinoma archived in Pathology Department of Cancer Institute, Tehran, Iran, from 2011 to 2014. Immunohistochemistry was applied to detect ER, PR, and Her-2. Results: The current study findings indicated a significant correlation of 90% between CNB and SE specimens for ER expression. The correlation between CNB and SE specimens was estimated as 81% and 97.3% for PR and Her-2, respectively. Discussion: CNB can be performed confidently to determine ER and Her-2. For PR, results obtained from CNB should be considered.
Azadeh Sadat Nazouri; omolbanin asadpour; Shahriar Dabiri; Bahram Pourseyedi; Mohamad reza Lashkarizadeh; Hamid Zeinalyneghad
Abstract
Background & objective: Breast cancer is the leading cause of cancer related death in females. Sphingosine kinase 1 (SPHK1) and its product sphingosine-1-phosphate (S1P) are the essential key regulator molecules in breast cancer through their ability to promote cell proliferation, angiogenesis, cell ...
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Background & objective: Breast cancer is the leading cause of cancer related death in females. Sphingosine kinase 1 (SPHK1) and its product sphingosine-1-phosphate (S1P) are the essential key regulator molecules in breast cancer through their ability to promote cell proliferation, angiogenesis, cell proliferation, and lymphagiogenesis. SPHK1 is overexpressed in multiple types of cancer including breast cancer and is associated with resistance to treatment. The current study aimed at investigating the expression of SPHK1 in estrogen and progesterone receptors (ER, PR) negative in comparison to ER, and PR positive breast cancer and their normal controls, and also finding the relationship between SPHK1 expression and high body index (BMI) in the selected groups with breast cancer. Methods: A total of 120 human breast cancer tissue specimens were analyzed for SPHK1 expression using quantitative real–time polymerase chain reaction (q RT-PCR) assay. Detection of hormonal status of breast cancer tissue samples was conducted by immunohistochemical assay. Result: The current study findings showed that the level of SPHK1expression in the breast cancer tissue was significantly higher in patients with estrogen and progesterone negative receptors, compared to the ones without them (P-value< 0.05). The obtained data confirmed that the obesity in patients with ER negative was higher than the ones with positive receptors (BMI> 25). Conclusion: The current study showed that expression of SPHK1gene was higher in the patients with ER and PR negative breast cancer and high BMI, compared with other groups.
Hematopathology
Hossein Ayatollahi; Azar Fani; Ehsan Ghayoor Karimiani; Fateme Homaee; Arezoo Shajiei; Maryam Sheikh; Sepideh Shakeri; Seyyede Fatemeh Shams
Abstract
Background and objective: The assessment of human epidermal growth factor receptor 2 (HER2) status has become of great importance in the diagnosis of breast cancer. The aim of this study was to investigate the diagnostic value of quantitative Polymerase Chain Reaction (qPCR) and Chromogenic In Situ Hybridization ...
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Background and objective: The assessment of human epidermal growth factor receptor 2 (HER2) status has become of great importance in the diagnosis of breast cancer. The aim of this study was to investigate the diagnostic value of quantitative Polymerase Chain Reaction (qPCR) and Chromogenic In Situ Hybridization (CISH) to assess HER2 status of biopsy specimens. Methods: To elucidate the status of HER2 gene amplification, biopsies of breast carcinoma from 120 patients with 2+ IHC status were analyzed by qPCR and CISH. Results: The results of the two experiments were compared, and it was depicted that the concordance rate between CISH and qPCR assays was 88.1%.The quantification of HER2 gene with CISH and qPCR showed that there was a significant correlation (p value= 0.0001 and r= 0.808). Conclusion: The results of this research support the idea that qPCR is a precise and reproducible technique, which can be employed as a supplementary method to evaluate HER2 status.
Biochemistry
Maryam Karimi; Hossein Babaahmadi-Rezaei; Ghorban Mohammadzadeh; Mohammad-Ali Ghaffari
Abstract
Background and objective: According to reports, a serine protease inhibitor (Maspin) suppresses metastasis, invasion and angiogenesis in breast and prostate cancers. Silibinin is a natural polyphenolic flavonoid with anti-cancer activity. We assessed the effects of silibinin on cell viability, maspin ...
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Background and objective: According to reports, a serine protease inhibitor (Maspin) suppresses metastasis, invasion and angiogenesis in breast and prostate cancers. Silibinin is a natural polyphenolic flavonoid with anti-cancer activity. We assessed the effects of silibinin on cell viability, maspin and ERα gene expression in MCF-7 cell line. Methods: The human MCF-7 breast cancer cell line was cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) and treated with different concentrations of silibinin (100-600 μg/mL) for 24, 48 and 72 hours. The cytotoxic effect of silibinin on MCF-7 viability was determined using Methyl-Thiazolyl-Tetrazolium (MTT) assay by IC50 determination. The fold changes of Maspin and ERα expression were determined by reverse-transcription real-time Polymerase Chain Reaction (PCR). All experiments on the cells were performed in triplicates. Results: The maximum inhibitory effect of silibinin on cell viability was observed at 600 μg/mL after 72-hour incubation (p = 0.001). Incubation of the cells with silibinin for 48 and 72 hours significantly decreased IC50 values to 250 and 207 μg/mL (p = 0.005 and p= 0.006), respectively. The expression of maspin and ERα in the treated cells compared to controls was significantly decreased following treatment with different concentrations of silibinin during a 24-hour period. Conclusions: Silibinin reduces both maspin and ERα gene expression in MCF-7 cell line. The therapeutic effect of silibinin on the treatment of breast cancer may be mediated by the reduction of ERα expression. For verifying this hypothesis and the possible therapeutic implication of silibinin on breast cancer, further studies in this direction are necessary.
Hematopathology
Fatemeh Homaei Shandiz; Azar Fani; Sepideh Shakeri; Maryam Sheikhi; Abouzar Ramezani Farkhani; Arezoo Shajiei; Hossein Ayatollahi
Abstract
Background:Breast cancer remains the most common and second lethal cancer in females. HER-2/neu is one of the most important amplified oncogene in breast cancer. The amplification of HER-2 is correlated with decreased survival, metastasis, and early recurrence. The amplification of HER-2/neu gene ...
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Background:Breast cancer remains the most common and second lethal cancer in females. HER-2/neu is one of the most important amplified oncogene in breast cancer. The amplification of HER-2 is correlated with decreased survival, metastasis, and early recurrence. The amplification of HER-2/neu gene and synthesis of the protein are reported in 10%-34% of breast cancer cases associated with tumor size, advanced tumor stage, high-grade tumor, young age at diagnosis, absence of steroid hormone receptor, and lymph node involvement. Methods: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods are options to evaluate HER-2 expression. The current study aimed at identifying the correlation between FISH and real-time polymerase chain reaction (PCR) in measuring HER-2 expression. Results: The study investigated the performance of the real-time PCR as measured against FISH method in IHC +2 borderline cases. In a total of 120 IHC 2+ samples, 58.3% were negative and 41.6% positive for HER-2 gene, confirmed by FISH as a gold standard method. The real-time PCR ratio was HER-2 gene by FISH as a gold standard assay. Conclusion: Despite the fact that real-time PCR is a promising method to evaluate HER-2 over expression and a supplementary array to FISH, according to the results of the present study it cannot be utilized instead of gold standard techniques; therefore, additional studies should be carried out to appraise the value of this method to evaluate HER-2 over expression.
Hematopathology
Payam Azadeh; Nasser Rakhashni; Ali Yaghobi Joybari; Pegah Gorji Bayani; Samaneh Sarbaz; Maryam Farasatinasab
Volume 11, Issue 5 , October 2016, , Pages 439-442
Abstract
The oral cavity is uncommon site for metastatic disease usually discovered secondary to malignancy. We encountered with a rare case in which metastasis to mandibular bone was the first clinical sign in the diagnosis of breast cancer without any radiographic findings. A 49-yr-old premenopausal woman, ...
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The oral cavity is uncommon site for metastatic disease usually discovered secondary to malignancy. We encountered with a rare case in which metastasis to mandibular bone was the first clinical sign in the diagnosis of breast cancer without any radiographic findings. A 49-yr-old premenopausal woman, was referred to the Department of Medical Oncology of Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran in 2014, presented with pain and tenderness in the left mandibular and temporal bone and paresthesia of the lower left lip and chin. CT scan of mandible showed no significant finding. Four months later, she was referred with complaints left breast pain for 4 wk and worsening swelling, pain and paresthesia. Breast examination revealed a 2 cm firm nodule on the left breast. Based on her medical history and histopathological study, metastatic carcinoma of the breast was suspected. She has received chemoradiotherapy that led to complete relief of her symptoms and remission of the disease. In the presence of an ambiguous sign in oral cavity such as jaw pain or paresthesia, diagnostic examination of malignancy is recommended.
Biology & Genetic
Shahriar Dabiri; Mohammadmehdi Moeini aghtaei; Jahanbano Shahryari; Manzume Shamis meymandi; Sahar Amirpour-Rostami; Reza Foutohi-Ardekani
Volume 11, Issue 2 , April 2016, , Pages 104-111
Abstract
Background: The breast cancer is the most prevalent cancer among women, on the other hand absence of myoepithelial cells play a pivotal role in pathogenesis of this cancer. Thus we aimed to investigate the possible abilities of the molecular assay technique to find a relationship between mammary serine ...
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Background: The breast cancer is the most prevalent cancer among women, on the other hand absence of myoepithelial cells play a pivotal role in pathogenesis of this cancer. Thus we aimed to investigate the possible abilities of the molecular assay technique to find a relationship between mammary serine protease inhibitor (Maspin) gene expression possibly secreted by myoepithelial cells, grade of breast cancer and other prognostics factors (ER, PR, and c-erb-B2). Methods: Paraffin embedded blocks of 31 breast cancer patients together with two normal breast tissues were used for IHC staining and Maspin gene RNA detection uses the real-time PCR method. Applying QIAGEN kit, we were able to measure Maspin RNA and Extract the cDNA of different samples for evaluating the Maspin RNA level. Results: We found that the RNA level was considerably lowerin these cancer samples compared with normal samples. In addition, different grades of breast cancer in the obtained results adopt some distinguishable values. The Maspin expression in samples with grades II and III is much lower than the ones in normal group (P<0.05) which could be considered as a promising way in diagnosing of this disease. The results showed no considerable differences in Maspin gene expression of the c-erb-B2 scores in the tumor group except the samples having score 0. The other observation of this research study confirmed that Maspin gene expression couldn't show any differences between the values of both ER and PR in different scores of the tumor group. On the other hand, the cDNA of these patients showed lower values compared with normal samples. Conclusion: Maspin expression was reduced in samples with grade II& III of invasive ductal carcinoma. Based on expression of Maspin Inc-erb-B2, it seems that more expression happened in normal group comparing with different scores of it. We could suggest that there was a reverse relationship between tumor formation and Maspin gene expression. These results showed possible role of Maspin as prognostic factor.
Masoumeh Salehpour; Naser Tayyebi Meibodi; Roghayeh Teimourpour; Adel Ghorani-Azam; Samaneh Sepahi; Sina Rostami; Zahra Meshkat
Abstract
Background &Objective: Breast cancer is the most common female malignancy. Detection of DNA of human papillomaviruses (HPVs) in breast carcinomas suggests that the virus may play a role in the pathogenesis of this disease. The aim of this study was to evaluate the frequency of HPVs genotypes 6, 11, ...
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Background &Objective: Breast cancer is the most common female malignancy. Detection of DNA of human papillomaviruses (HPVs) in breast carcinomas suggests that the virus may play a role in the pathogenesis of this disease. The aim of this study was to evaluate the frequency of HPVs genotypes 6, 11, 16, 18 and 31 in paraffin-embedded tissue samples of invasive breast carcinomas. Methods: Three hundred and twenty six paraffin-embedded tissue samples of breast cancer were studied. PCR was performed using specific primers for HPV genotypes. Results: Of total 206 (63.2%) samples positive for Beta-globin gene, 54 (26.2%) were HPV-positive and 152 (73.8%) were negative for HPV. Distribution of HPV genotypes were as follows: 19 (25.7%) were positive for genotype 11, 5 (6.8%) were positive for genotype 6; and 2 cases (2.7%) were positive for both genotypes 6 and 11. Samples were also screened for HPV genotypes 16, 18 and 31 but none was positive. Conclusion: The current study confirmed the association of HPV and breast cancer. However, all samples were negative for high-risk HPV types 16, 18 and 31. How to cite this article: Salehpour M, Tayyebi Meibodi N, Teimourpour R, Ghorani-Azam A, Sepahi S, Rostami S, et al. Frequency of Human Papillomavirus Genotypes 6, 11, 16, 18 And 31 in Paraffin-Embedded Tissue Samples of Invasive Breast Carcinoma, North-East of Iran. Iran J Pathol. 2015;10(3):192-8.
Fahimeh Mousavi; Mehrdad Noruzinia; Elahe Keyhani; Feridoon Seirati; Samira Rezaei; Forough Mojtahedi; Farkhondeh Behjati
Volume 9, Issue 2 , April 2014, , Pages 117-123
Abstract
Background and Objective: The DBC2 (deleted in breast cancer 2) or RhoBTB2 (Located on 8p21) is a tumor suppressor gene associated with tumorigenesis. Mutational studies of DBC2 at its promoter region in breast cancer revealed an important role for epigenetic changes contributing to its low expression. ...
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Background and Objective: The DBC2 (deleted in breast cancer 2) or RhoBTB2 (Located on 8p21) is a tumor suppressor gene associated with tumorigenesis. Mutational studies of DBC2 at its promoter region in breast cancer revealed an important role for epigenetic changes contributing to its low expression. Epigenetic changes through hypermethylation of the promoter can cause the inactivation of DBC2 gene. The purpose of this study was to investigate methylation pattern of DBC2 gene in the peripheral blood of 40 Iranian women with breast cancer and its comparison with healthy women.
Material & Methods: We used peripheral blood samples from 40 patients with sporadic breast cancer and 40 normal individuals. Analysis of the methylation statues of DBC2 promoter region was done by MSP (Methylation Specific PCR ) technique on the DNA extracted from the blood samples. The results were validated by sequencing. The methylation status was then correlated with the clinicopathological parameters of breast cancer patients.
Results:Methylation pattern was detected in 60% of the patients, whereas 25% of the normal individuals demonstrated a positive methylation pattern (P ≤ 0.01, odd ratio : 2.143). No significant correlation was obtained between methylated DBC2 and cliniclpathological parameters.
Discussion: Aberrant hypermethylation was observed preferentially in the patients. These findings along with the previous studies, propose that abnormal methylation pattern in DBC2 promoter region may be one of the main reasons for low expression of DBC2 in breast cancer and this hypermethylation pattern could play a fundamental role in the breast tumorigenesis.
Ali Zare Mehrjardi; Amineh Vaghefi
Volume 8, Issue 1 , January 2013, , Pages 27-35
Abstract
Background & Objectives: Anaplastic lymphoma Kinase (ALK) is a receptor tyrosine kinase involved in the genesis of several human cancers. ALK was initially identified because of its involvement in anaplastic large cell lymphoma (ALCL). ALK is believed to foster tumorigenesis following activation ...
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Background & Objectives: Anaplastic lymphoma Kinase (ALK) is a receptor tyrosine kinase involved in the genesis of several human cancers. ALK was initially identified because of its involvement in anaplastic large cell lymphoma (ALCL). ALK is believed to foster tumorigenesis following activation by autocrine and/or paracrine growth loops. Studies reveal that the presence of anti-ALK antibodies may be relevant to the relatively good prognosis. Therapeutic approaches consisting of gene therapy and immunotherapy targeting this molecule hold promise.
Material & Methods: We examined a number of human breast cancers to see if ALK is expressed in this tumor and studied its relation with type of carcinoma and its grade, tumor size, presence of necrosis, vascular invasion , skin involvement, lymph node metastasis and patient’s age.
Result: 100 patients were enrolled with mean age of 50.2 ± 12.5 years. The histological phenotypes of the breast cancers studied included Invasive Ductal Carcinoma, Invasive Lobular Carcinoma and Medullary Carcinoma. ALK expression was evaluated by immunohistochemistry which was positive in 47 cases (47%). No statistically significant relationship is found between the above mentioned parameters except for tumor size and ALK expression. (P< 0.01)
Fatemeh Mahjoub; Farrokh Tirgari; Afshin Abdi Rad; Mahmoud Mohammadi; Nargess Tabarzan; Omid Emadian
Volume 3, Issue 2 , March 2008, , Pages 95-99
Abstract
Background and Objective: Male breast carcinoma (MBC) is an unusual form of neoplasia, representing 0.7 to 1 percent of all breast cancer cases. Usually, the carcinoma affects patients after the sixth decade. The aim of this study was to evaluate the status of estrogen and progesterone receptors (ER ...
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Background and Objective: Male breast carcinoma (MBC) is an unusual form of neoplasia, representing 0.7 to 1 percent of all breast cancer cases. Usually, the carcinoma affects patients after the sixth decade. The aim of this study was to evaluate the status of estrogen and progesterone receptors (ER and PR) and prognostic factors (p53 and Her-2/neu) in a series of male patients with breast cancer and correlate them with tumor grade and stage. Materials and Methods: Fifty cases of breast carcinoma in male patients, retrieved from the files of the Cancer Institute from 1996 until 2005 was included in this study. Results: Most of the cases were categorized as grade 2 (65.3%), grade 1 cases comprised 20.4% and grade 3 was 14.3%. Stage IIb was the largest group (32%). Estrogen receptor was detected in 90% of cases and progesterone receptor in 68% of cases and no significant correlation was found between estrogen and progesterone receptor positivity and tumor grade or stage. In addition, p53 and Her-2/ neu staining revealed positivity in 11 cases (27.5% ) and 13 cases (26%) respectively with strong positivity in only 6 cases and no significant correlation was found between tumor grade and stage and p53 expression. It is clear from our data that Her-2/neu positivity in MBC is lower than in female breast carcinoma. Conclusion: This study, which comprises rather large series of MBC in Iran during a 10-year period, shows that most patients refer in rather late stages and prognostic factors such as p53 and Her-2/neu has no significant correlation with tumor grade and stage at presentation in our patients.
Nasrin Shayanfar; Behrang Kazeminejad
Volume 3, Issue 1 , January 2008, , Pages 30-34
Abstract
Background and Objective: Determination of hormone receptor status in the management of breast cancer is well-established. The aim of this study was to evaluate the frequency of androgen receptor (AR) expression in invasive ductal carcinoma of breast. Materials and Methods: For this purpose, ...
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Background and Objective: Determination of hormone receptor status in the management of breast cancer is well-established. The aim of this study was to evaluate the frequency of androgen receptor (AR) expression in invasive ductal carcinoma of breast. Materials and Methods: For this purpose, 55 cases of invasive ductal breast carcinoma were examined using a monoclonal antibody against AR on formalin-fixed paraffin-embedded archival material. The results were correlated with the results of estrogen and progesterone receptors (ER and PR) previously done immunohistochemically on the specimens. Results: It was found out that AR was positive in 24 cases (43.6%). In addition, AR was positive in 33% (3) of grade 1, 45% (16) of grade 2, and 38% (15) of grade 3 tumors. Previously, ER and PR were done on 34 cases including 5 grade 1, 18 grade 2, and 11 grade 3 carcinomas. Among the grade 1 cases, 2 out of them were AR positive which were also ER and PR positive but 2 (11%) out of grade 2 and 3 (27%) out of grade 3 tumors were AR positive and ER negative. Also, 5 (28%) out of grade 2 and 3 (27%) out of grade 3 tumors were AR positive and PR negative. In grade 2 tumors, correlation between ER and PR negativity with AR positivity was significant. Conclusion: AR expression is common in invasive breast carcinomas. Some high grade carcinomas are ER and PR negative and AR positive. We suggest that immunohistochemical evaluation of AR may help in providing more information about steroid receptors in breast carcinomas
Farid Moinfar
Volume 2, Issue 4 , September 2007, , Pages 127-143
Abstract
This review deals with studies that have used cDNA microarrays and immunohistochemistry to identify a subtype of breast carcinoma recently known as “basal-like” carcinoma. The key breast carcinoma studies are critically discussed to highlight methodological problems in cohort selection, definitions, ...
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This review deals with studies that have used cDNA microarrays and immunohistochemistry to identify a subtype of breast carcinoma recently known as “basal-like” carcinoma. The key breast carcinoma studies are critically discussed to highlight methodological problems in cohort selection, definitions, interpretation of results, and statistical analysis. It concludes that “basal-like” carcinomas do not reflect a single, biologically uniform group of breast cancers and show significant variations in their phenotypes, grades, immunoprofiles, and clinical behavior, just as a wide range of subtypes and behaviors is observed among epithelial/luminal-derived breast carcinomas. Welldesigned studies with comparison of low grade non-basal versus low grade basal and high grade non-basal versus high grade basal carcinomas are necessary before one can be convinced that this subtype represents a distinct clinicopathologic entity.
