Positive Androgen Receptor Expression Research Articles

Correlation of Expression of Androgen Receptors and P16 in Triple Negative Breast Carcinoma - A Five Years Retrospective and Prospective Study

AIM AND OBJECTIVE Triple negative breast carcinoma (TNBC) is an aggressive breast carcinoma, lacking estrogen receptor (ER),progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2neu receptor) amplification, thereby, unresponsive to conventional hormonal therapy. The aim of present study is to examine androgen receptor (AR) and p16 expression in TNBC cases and explore its clinical significance in view of potential AR and p16 targeted TNBC therapy. MATERIAL AND METHOD A total 94 TNBC patients were included in this 5 years (3 years retrospective and 2 years prospective) study, conducted at Department of Pathology, JNMCH, Aligarh. Immunohistochemical stains for AR and p16 were performed and their relationship with TNBC clinicopathological data were analyzed. Positive AR expression was defined as ≥1% nuclear staining wheras positive p16 expression was defined as score of ≥1which in turn calculated as product of intensity score and extent of positivity score of cytoplasmic and nuclear stained cells. RESULT Out of 94 TNBC patients, 92 cases were of invasive carcinoma (NST) and 2 cases were invasive lobular carcinoma.AR was expressed in 38/94 (40.4%) cases, all of which were of invasive carcinoma (NST) type. We observed higher expression rate in postmenopausal women i.e.43.2% (16/37) cases and in patients with age ≥60 years i.e. 66.7% (8/12) cases. Statistical analysis showed significant association of AR + TNBC cases with larger tumor size (p= 0.017412) and lymph node metastases (p= 0.033119). Higher expression rate was found in lower grade and stage III, however statistically insignificant.p16 protein was positively expressed in 72.3% (68/94) of the total TNBC cases. We observed higher expression rate in premenopausal women i.e.78.9%(48/57) cases and in patients with age 40-49 years i.e. 84.4% (27/32) . Significantly higher p16 expression rate was found in grade II (90%) followed by grade I (66.7%) and grade III (65%) (p= 0.04). CONCLUSION TNBC was more common in older age group and had a higher propensity for lymph node metastases. AR positive and p16 positive TNBC cases may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapy.

Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival.

Breast cancer in older women tends to have more favourable biology, compared to younger women. Androgen receptor (AR) is significant for breast tumour carcinogenesis; however, the role of AR in older women has not been fully explored. Surgical specimens were obtained from an existing series of 1758 older women (≥ 70years) with primary breast cancer, treated in a single institution with long-term (≥ 37years) follow-up. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and a panel of 24 biomarkers was measured by immunohistochemistry (IHC) in these TMAs. AR positivity was assessed by IHC and defined as H-score ≥ 40. The relationship between AR in this cohort was compared to an equivalent group of younger women (< 70years, n = 1708); the panel of 24 biomarkers and breast cancer specific survival (BCSS) in the older cohort. AR was assessed in 509 samples. Overall, 59% of the older women cohort had positive expression of AR, compared to 63% in the younger cohort. AR positivity (regardless of age) was associated with smaller size of tumour, lower grade of tumour, lower tubule formation, lower nuclear polymorphism and lower mitotic frequency. AR positivity was associated with positive expression of oestrogen receptor (ER), progesterone receptor (PR), breast cancer gene1 (BRCA1), cytokeratin (CK) 7/8, CK18, CK19, Bcell lymphoma (Bcl)2 and Mucin1 (Muc1) expression. Conversely, AR-positive expression was associated with negative expression of human epidermal growth factor receptor2 (HER2), Ki-67, CK5, CK17, epidermal growth factor receptor (EGFR), and CD44 expression. Older women with AR-positive tumours had better BCSS compared to AR-negative tumours (p = 0.009). There was no difference in AR expression between older and younger women with breast cancer. AR has prognostic potential in terms of BCSS. Further work is needed to investigate AR as a therapeutic target.

Correlation of androgen receptor with ultrasound, clinicopathological features and clinical outcomes in breast cancer

BackgroundThis study aimed to explore whether there is an association between androgen receptor (AR) expression and ultrasound, clinicopathological features and prognosis of breast cancer.MethodsA total of 141 breast cancer patients were included in this retrospective study. AR expression was analyzed by immunohistochemistry. The images of B-mode, color Doppler and strain elastography from 104 patients were collected continuously, and the corresponding ultrasound characteristics were obtained. The differences in ultrasound and clinicopathological features in different AR status were analyzed. Progression-free survival (PFS) of patients was obtained through up to 90 months of follow-up; then, the effect of AR on PFS was analyzed. Subsequently, a nomogram was constructed to predict the AR status. The predictive accuracy was calculated using C-index.ResultsThe positive expression of AR (AR +) was associated with lower histological grade (p = 0.034) and lower Ki-67 level (p = 0.029). Triple-negative breast cancer (TNBC) had the lowest probability of AR + (p < 0.001). The AR + group mostly showed unsmooth margin (p < 0.001), posterior acoustic shadowing (p = 0.002) and higher elasticity score (p = 0.022) on ultrasound. The echo pattern of most tumors with AR + was heterogeneous (p = 0.024) in Luminal A subtype. AR + could be a sign of a better prognosis in overall breast cancer (p < 0.001), as well as in human epidermal growth factor receptor 2 (HER2) overexpression and Luminal B subtypes (p = 0.001 and 0.025). The nomogram showed relatively reliable performance with a C-index of 0.799.ConclusionOur research demonstrated that AR expression was closely related to ultrasound, clinicopathological features and prognosis of breast cancer.

The Prognostic Values of Androgen Receptor in Breast Cancer.

Whether androgen receptor (AR) expression can predict prognosis in breast cancer is under debate. To analyze, retrospectively, the prognostic and treatment-predictive ability of AR status in breast cancer. A total of 5765 patients diagnosed with primary invasive breast cancer without distant metastasis in the adjuvant setting were analyzed. The propensity score-matching method was used to develop a new cohort of 3978 patients (1989 patients each) in which important prognostic factors were balanced. Positive AR expression is an independent prognostic factor for disease-free survival and overall survival. Estrogen receptor (ER)+ and progesterone receptor (PR)+ AR+ breast cancer patients had the longest survival, whereas ER-PR-AR- breast cancer patients had the shortest survival. The ER/PR/AR combinations could not predict the treatment effects for adjuvant trastuzumab but could be used for adjuvant chemotherapy and endocrine therapy selection. The worst survival was found in ER+PR-AR- patients receiving toremifene, ER+PR-AR+ patients receiving exemestane, ER+PR+AR- patients receiving anthracycline, and ER-PR-AR+ patients receiving taxanes. ER+PR-AR-, ER-PR-AR+, and ER-PR-AR- patients were associated with the worst survival among those who received radiotherapy and anthracycline plus taxanes. AR in combination with ER and PR could predict the prognosis and treatment effects of chemotherapy, endocrine therapy, and radiotherapy in the adjuvant setting.

The expression of androgen receptor in triple-negative breast cancer and the effect of a traditional Chinese medicine formula on disease-free survival

Androgen receptor (AR) is becoming an important factor in the pathogenesis of breast cancer. Traditional Chinese medicine (TCM) is widely used in treating breast cancer patients. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which has worse prognosis than other subtypes. Herein, through this retrospective study, we summarize the therapeutic implications of AR and TCM in TNBC. The clinical and pathological data of TNBC patients who had undergone surgery at The First Affiliated Hospital of Zhejiang Chinese Medical University from 2017 to 2019 were collected and examined. The t-test, chi-square test, logistic regression model, and Kaplan-Meier survival estimates were used to analyze the data. We identified 823 early breast cancer patients from January 2017 to December 2019, of whom 92 (11.2%) were pathologically confirmed to have TNBC. We excluded 5 patients according to the inclusion and exclusion criteria. In relation to the remaining 87 patients, 33 (37.9%) were AR positive. In the TNBC patients, positive AR expression was correlated with an older age (P=0.006), a higher weight (P=0.006), and lower Ki-67 expression (P=0.031). After a median follow-up time of 37 months (range, 24-60 months), 13 cases of relapse and metastasis (14.9%) were observed. We found that relapse and metastasis were correlated with being unmarried [P=0.004; hazard ratio (HR) =0.105; 95% confidence interval (95% CI): 0.023-0.487], nonporous (P=0.046; HR =0.209; 95% CI: 0.045-0.971), and negative AR expression (P=0.042; HR =1.223; 95% CI: 0.049-1.012). The AR-positive TNBC patients had better disease-free survival (DFS) than the AR-negative TNBC patients 2-5 years after surgery (P<0.05). TCM was an effective treatment for TNBC (P<0.001; HR =51.682; 95% CI: 6.660-401.025). In the AR-negative group, patients who received the TCM treatment tended to have a better DFS than those who did not receive the TCM treatment (P<0.001; HR =34.832; 95% CI: 4.448-272.756); however, no such difference was found in the AR-positive group. The TNBC patients with positive AR tended to have a low expression of Ki-67 and a better prognosis than AR negative TNBC patients. TCM is an effective treatment and has slight side effects.

PARP1, BRCA1 and androgen receptor expression in triple-negative breast cancer patients treated with neoadjuvant chemotherapy

IntroductionTriple-negative breast cancer (TNBC) is an aggressive subtype, where no effective therapies have been established for it. Searching for therapeutic targets for TNBC patients is the aim of the current research. Poly adenosine diphosphate ribose polymerase (PARP1) inhibitors are promising antitumor therapy that have a high potency in BRCA1-deficient breast cancers. Materials and methodsForty TNBC patients who received neoadjuvant chemotherapy (NAC) were enrolled in this study, and evaluated for PARP1, BRCA1, and Androgen receptor (AR) immunohistochemical expression before and after receiving NAC. Data of patients' clinical and pathological responses to the chemotherapy were collected and finally analyzed. ResultsThe immunohistochemical results revealed 10 cases (25%) positive for AR, while 18 cases (45%) and 22 cases (55%) expressed PARP1 at low and high levels, respectively. Twelve cases (30%) and 28 cases (70%) expressed BRCA1 at low and high levels, respectively. There was a significant difference between PARP1 expression in normal and malignant tissues (P < 0.001). Higher PARP1 expression was correlated with a better overall clinical response (OAR) and pathological complete response (pCR) (P = 0.018, 0.01 respectively). Co-expression of both PARP1 & BRCA1 was correlated with OAR and pCR. Chemotherapy decreases PARP1 protein levels in matched patient samples (P = 0.015). Positive AR expression was correlated with BRCA1 overexpression. ConclusionPARP1 is highly expressed in TNBC with a better OAR and pCR especially in cases with high BRCA1, so it might be considered as a therapeutic target for this risky group.

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer.

Novel immune checkpoint-based immunotherapies may benefit specific groups of prostate cancer patients who are resistant to other treatments. We analyzed by immunohistochemistry the expression of B7-H3, PD-L1/B7-H1, and androgen receptor (AR) in tissue samples from 120 prostate adenocarcinoma patients treated with radical prostatectomy in Spain, and from 206 prostate adenocarcinoma patients treated with radical prostatectomy in Norway. B7-H3 expression correlated positively with AR expression and was associated with biochemical recurrence in the Spanish cohort, but PD-L1 expression correlated with neither of them. Findings for B7-H3 were validated in the Norwegian cohort, where B7-H3 expression correlated positively with Gleason grade, surgical margins, seminal vesicle invasion, and CAPRA-S risk group, and was associated with clinical recurrence. High B7-H3 expression in the Norwegian cohort was also consistent with positive AR expression. These results suggest distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer. Our findings highlight B7-H3 as an actionable novel immune checkpoint protein in prostate cancer.

Neoadjuvant targeted therapy for apocrine carcinoma of the breast: A case report

BACKGROUNDApocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice. Neoadjuvant therapy, especially neoadjuvant targeted therapy, has rarely been reported for apocrine carcinoma of the breast.CASE SUMMARYA 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy. The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status (estrogen receptor and progesterone receptor) but showed overexpression of human epidermal factor receptor 2 (HER-2). Moreover, positive expression of androgen receptor (approximately 60%) and gross cystic disease fluid protein 15 was observed. The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen (docetaxel, carboplatin area under curve 6 and trastuzumab) every 21 d. The mass in the left breast was significantly reduced, and pain in the breast and left upper arm also improved.CONCLUSIONHER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.

Clinicopathologic Parameters and Survival Data in Non-Metastatic Breast Cancer Patients in Correlation with Tumour Infiltrating Lymphocytes, Androgen Receptor and Insulin-Like Growth Factor Receptor 1 Expression

Introduction: The constantly evolving nature of breast cancer (BC) makes it paramount to identify and evaluate more biomarkers that may have a predictive and prognostic value. We explored the relationship between the androgen receptor (AR), insulin-like growth factor 1 receptor (IGF-1R) and tumour infiltrating lymphocytes (TILs), and clinicopathologic variables and survival in BC. Materials and Methods: In this retrospective study, we collected clinical and pathological data of 105 BC patients who had been treated at Alexandria Main University Hospitals from January 2010 to December 2016. These patients’ formalin fixed paraffin-embedded blocks were retrieved and analyzed for AR and IGF-1R expression immunohistochemically; TILs were assessed by hematoxylin and eosin staining. Chi square and Kaplan Meier curves were used to study the correlation between the three biomarkers and clinicopathologic parameters and survival respectively. Results: 59% and 51.4% of patients were AR and IGF-1R positive respectively. AR immunoreactivity correlated with a tumour size less than 5 centimeters (p=0.001), presence of carcinoma in situ (p=0.008), negative Her 2 status (p=0.007) and negative lymphovascular invasion (p&lt;0.001). Negative AR expression predicted a longer disease free survival (p=0.017). A positive IGF-1R was associated with carcinoma in situ (p&lt;0.001) and negative extra-nodal extension (p=0.042) but no impact on the disease free survival (p=0.227). A high TIL expression was associated with a tumour size less than 5 centimeters (p=0.005), invasive lobular carcinoma (p=0.006), carcinoma in situ (p=0.047), negative LVI (p&lt;0.001) and longer survival. A positive AR expression was associated with a positive IGF-1R expression (p&lt;0.001). Conclusions: AR, IGF-1R and TILs correlate differently with various clinicopathologic variables used in BC; in addition they all have a prognostic value. The two receptors are a promising target in BC. More clinical studies are required to further confirm the utility of these three biomarkers.

The Association of Androgen Receptor Expression with Renal Cell Carcinoma Risk: a Systematic Review and Meta-Analysis.

The relationship between androgen receptor expression and renal cell carcinoma risk remains controversial. This study is aimed to investigate the clinical significance of androgen receptor expression in renal cell carcinoma. A computerized bibliographic search of Embase, the PubMed, and Web of Science combined with manual research between 1977 and 2017 was conducted to explore the association between androgen receptor expression and clinicopathological features of renal cell carcinoma. Data were analyzed by a meta-analysis using RevMan 5.3 analysis software. Eleven retrospective studies with 1839 renal cell carcinoma cases were finally included according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. It was found that there was no significant difference between androgen receptor expression and susceptibility, pathological type, metastatic status, metastatic type (lymph or distant metastasis) and cancer-specific survival of renal cell carcinoma (P > 0.05). However, positive androgen receptor expression was demonstrated to be significantly associated with male patients, lower pathological grade, and earlier tumor stage of renal cell carcinoma (OR = 1.69, 95% CI = 1.30-2.19, P < 0.0001; OR = 2.06, 95% CI = 1.49-2.85, P < 0.0001; OR = 2.81, 95% CI = 1.30-6.12, P = 0.009; respectively). In conclusion, higher androgen receptor expression was correlated with male patients, low tumor grade and early stage of renal cell carcinoma. Based on current results, androgen receptor-inhibited target therapy for renal cell carcinoma patients may be of limited benefits and should be taken into more evaluations.

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER- breast cancer.

The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor-negative (ER- ) breast cancer (BC) is undetermined. Prostate-derived ETS factor (PDEF) is highly restricted to the hormone-regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER- BC. We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER- invasive BC, and investigated their relationship in ER- BC cell lines. The expression of PDEF was associated with the positive expression of AR (P<0.001) and a worse survival rate (P=0.006). PDEF+ tumours were significantly more often AR+ (P<0.001). AR and PDEF were more often co-expressed and the series of AR+ PDEF+ (126 of 246, 51.2%) had a poor survival rate (P=0.046). In Cox models, PDEF expression (P=0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR. PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER- BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER- breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER- BC.

The Relationship Between Androgen Receptor, Components of Tumour Microenvironment and Survival in Breast Cancer Molecular Subtypes

Background: The androgen receptor (AR) pathway has emerged as a potential therapeutic target in breast cancer with increased attention to provide biological insight into triple negative breast cancer (TNBC). The present study assessed the role of AR within the tumour microenvironment in patients with invasive ductal breast cancer. Methods: Immunohistochemical analysis of AR was performed on a breast cancer tissue microarray of 850 patients. These results were correlated with clinicopathological data and cancer specific survival (CSS). Results: Positive AR expression was seen in 75% of luminal A, 70% of B, 47% of Her2 like and 31% of TNBC. AR was associated with invasive grade (p<0.001), estrogen receptor /progesterone receptor (p<0.001), molecular subtypes (p<0.001), necrosis (p<0.001), reduced inflammation (p<0.001), and increased tumour budding (p=0.001). AR was consistently associated with tumour budding in molecular subtypes; luminal A (p=0.022), Her2 like (p=0.035) and TNBC (p=0.034). In TNBC, AR was associated with poor CSS (P=0.013). Conclusion: AR may be an important regulator of tumour budding in breast cancer. AR is a potential prognostic marker and therapeutic target for patients with TNBC.

Androgen Receptor Predicts First and Multiple Recurrences in Non-Muscle Invasive Urothelial Carcinoma of the Bladder.

The aim of this study is to investigate the role of androgen receptor (AR) expression on clinicopathologic characteristics, first recurrence free survival (RFS), progression free survival (PFS) and multiple recurrences in non-muscle invasive bladder cancer (NMIBC). AR expression in 40 paraffin-embedded specimens of primarily diagnosed NMIBC after transurethral resection was examined by immunohistochemistry using a monoclonal AR antibody. Associations between AR expression and clinicopathologic features and prognosis were statistically assessed. Multivariate Cox proportional hazards model was applied for evaluating predictive factors on RFS and PFS. For multiple recurrences, we used the Andersen-Gill model. AR was positive in 20/40 (50%) cases. Twenty-three patients (57.5%) had no recurrence, 10 (25.0%) had one recurrence, and 7 (17.5%) experienced more than one recurrence. AR expression and clinicopathologic features were not significantly correlated (P >0.05). Univariate analyses showed that AR expression was significantly associated with RFS and PFS (P <0.05). Via multivariate analyses, positive AR expression was significantly associated with lower risk of first recurrence (hazard ratio (HR) = 0.265; 95% confidence interval (95% CI) = 0.084-0.829; P = 0.022). Multivariate analysis of PFS was not feasible in our cohort. Using the multivariate Andersen-Gill model, positive AR expression in the primary tumor was an independent factor predicting lower risk of multiple recurrences (HR = 0.387, 95% CI = 0.161-0.927, P = 0.033). Androgen receptor expression is associated with first and multiple recurrences in NMIBC.

Androgen receptor expression in hormone-negative breast cancers and its prognostic significance

Background/aim Breast carcinoma is a common, yet heterogeneous aggressive disease affecting relatively young patients. The androgen receptor (AR) is expressed in majority of breast cancers and across the main breast cancer subtypes. The aim of this study was to evaluate AR expression in hormone-negative breast cancer subtypes. Materials and methods Sixty cases of breast cancer were involved in this study; the samples were received in the Department of Pathology of Kasr El-Aini Hospital, Cairo University, Egypt. The expression of AR and human epidermal growth factor receptor-2 receptors were studied by immunohistochemistry in 60 formalin-fixed paraffin-embedded selected hormone-negative breast cancer surgical specimens. The immunohistochemistry expression of the marker was correlated with the clinicopathological variables. Results Of the hormone-negative cases, 61.6% show positive AR expression, 89% of which are invasive duct carcinoma, 68.3% are associated with ductal carcinoma in situ, and 55% are human epidermal growth factor receptor-2-enriched subtype. A significant correlation was found between the AR expression and tumor type. There is no evident significant correlation with tumor grade, multicentricity or lymphovascular invasion. Conclusion The AR has recently emerged as a useful marker for the further refinement of breast cancer subtype classification. Antiandrogens are thought to markedly enhance treatments and to be the first targeted therapy in hormone-negative breast cancer cases.

Abstract 5802: Role of mesenchymal stem cells in acquisition of metaplasia in AKU-BC42 breast metaplastic carcinoma cell line

Abstract Introduction: Metaplastic carcinoma (MCa) is a rare and aggressive subtype of invasive breast carcinoma exhibiting epithelial to mesenchymal transition (EMT) where tumor of epithelial origin manifests differentiation into non-glandular, mesenchymal phenotypes such as spindloid, chondroid or osseous components. Acquisition of EMT is associated with low expression of e-cadherin, claudins and high expression of vimentin. Biological mechanisms for acquisition of metaplastic components within MCa are not well understood. The present study was undertaken to establish and characterize a cell line from a patient diagnosed with MCa and to evaluate the role of mesenchymal stem cells (MSC) in attainment of metaplastic phenotype. Methodology: AKU-BC-42 was established from a 65 years old Pakistani female patient diagnosed with T4N1M0 MCa. Specimen was procured and processed under sterile conditions and cultured in DMEM supplemented with 10% FBS. Epitheloid colonies were visualized after 3 weeks of culture, which were passaged and propagated. AKU-BC-42 was phenotypically and genotypically characterized using karyotyping, gene expression analysis, immunocytochemistry and florescent insitu hybridization. MSC marker expression was assessed by flow-cytometry. AKU-BC-42 was cultured under appropriate conditions for assessment of differentiation along osteogenic, adipogenic and chondrogenic pathways. Lineage differentiation was evaluated by special immunohistochemical stains and induction of lineage differentiation genes was assessed by Q-PCR. Results: AKU-BC-42 was found to have a human karyotype with multiploidy and population doubling time of 60 hours. Gene expression profiling revealed negative expression for estrogen and progesterone receptors and positive expression of androgen receptor (AR) and HER-2/neu. FISH analysis was negative for HER-2/neu amplification. Basal (5, 14 &amp; 19) and luminal cytokeratins (8 &amp; 18) were expressed at mRNA level along with myoepithelial markers (CD10, S100A7, p-cadherin, desmin, S100A4, S100A2 &amp; á-SMA). AKU-BC-42 demonstrated MSC pool with expression of CD73 (79.2%), CD90 (10.3%) and CD105 (30.2%) as revealed by flow-cytometry. Osteogenic differentiation was assessed by von kossa stain for mineralization with up-regulation of ALPL and OPN genes. Similarly, differentiation of AKU-BC-42 into mature adipocytes was evaluated with Oil red O staining of lipid droplets and expression of FABP4 gene. Chondrogenic induction was achieved by performing pellet cultures. Collagen synthesis in extracellular matrix of chondrogenic beads was assessed by mason trichrome staining with up-regulation of ACAN, COL10A1 and COMP. Conclusions: We report a novel MCa cell line containing a MSC pool. MSC pool within MCa may be responsible for acquisition of metaplasia in this rare subtype of breast cancer. Further studies on this cell line may reveal the biological mechanisms of MCa of the breast. Citation Format: Nazia Riaz, Sadia Habib, Azhar Hussain, El-Nasir Lalani. Role of mesenchymal stem cells in acquisition of metaplasia in AKU-BC42 breast metaplastic carcinoma cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5802. doi:10.1158/1538-7445.AM2017-5802

Expression of androgen receptor and embryonic stem cell associated transcript 4 in breast cancer patients with over-expression of human epidermal growth factor receptor 2 and their clinical significances

Objective To investigate the expression and clinical significance of androgen receptor(AR) and embryonic stem cell associated transcripts 4 (NANOG) in breast cancer patients with human epidermal growth factor receptor 2 (HER-2) over-expression, and to analyze its relationship with clinicopathologic features of breast cancer. Methods 143 breast cancer patients with HER-2 over-expression were selected from the screening of 1 052 cases of invasive breast cancer according to estrogen receptor (ER), progesterone receptor (PR) and HER-2 status. The protein expression of AR and NANOG was assayed by using immunohistochemistry.The relationship between AR expression and clinicopathological features was analyzed by χ2 test. The correlation between AR expression and NANOG expression was analyzed by Spearman correlation analysis. Results The positive expression of AR was 35.7% (51/143). The AR expression was not associated with age and menstruation status (both P > 0.05), and was associated with tumor size, clinical TNM staging and lymphatic metastasis (all P < 0.05). The positive rate of NANOG were 53.1% (76/143), and NANOG proteins were negative in adjacent normal breast tissue and benign breast lesions. The positive rate of AR was 27.6% (21/76) in NANOG-positive cases, whereas the positive rate of AR was 44.8% (30/67) in NANOG-negative cases, and the difference was statistically significant (χ2= 4.526, P= 0.033). There was an inverse correlation between NANOG and AR expressions (r=-0.255, P= 0.002). Conclusion AR and NANOG may be new targets for endocrine therapy and molecular biological therapy. Key words: Breast neoplasms; Receptor, epidermal growth factor; Androgen receptor; Embryonic stem cell associated transcripts 4; Immunohistochemistry

Mammary and Extramammary Paget's Disease Presented Different Expression Pattern of Steroid Hormone Receptors.

Background and Objectives Paget's disease (PD) is a rare intraepithelial adenocarcinoma, which is composed of mammary (MPD) and extramammary Paget's disease (EMPD). Currently, the published literature contains scant data on expression pattern of steroid hormone receptors in MPD and EMPD. Methods Expression of estrogen receptor (ER) and androgen receptor (AR) was evaluated in 88 MPD and 72 EMPD by using immunohistochemical staining and H-score method. Results Positive expression of AR was significantly higher in EMPD (61.11%, 44/72) than in MPD (32.95%, 29/88) (P < 0.001), while ER expression was positive 19.44% (14/72) in EMPD and only 9.09% (8/88) in MPD (P = 0.059). ER-AR expression pattern was significantly different between MPD (3.41%, 3/88) and EMPD (16.67%, 12/72) (P < 0.001). No difference of AR (P = 0.301) or ER (P = 0.239) expression was identified between invasive (48.57%, 51/105 of AR, and 11.43%, 12/105 of ER) and noninvasive PD. In MPD, no difference of AR expression between MPD alone (7/18, 38.89%) and MPD with underling ductal carcinoma of breast (22/70, 31.43%) was identified (P = 0.548). In EMPD, expression of AR was 63.33% (38/60) in penoscrotal EMPD. Conclusion Our current results indicate that MPD and EMPD presented different expression pattern of AR and ER and would help to further identify the molecular subtype of MPD and EMPD for adjuvant hormonal therapy, especially for patients with penoscrotal EMPD.

Androgen receptor in triple negative breast cancer: Expression and its clinic-pathological feature.

e12567Background: concern is now focused in the prognostic and predictive value of androgen receptor (AR) in breast cancer. Its expression and effect are variable and may depend on co-expression of estrogen receptor. The purpose of this study to investigate the expression of AR and its clinic-pathological feature in triple negative breast cancer. Methods: this retrospective study included 65 patients with TNBC. Who were treated in Ain Shams university hospital from January 2010 to December 2012 .paraffin blocks were retrieved and correlation between AR expression using immunohistochemistry and patient's clinico- pathological variables as well as survival . The cut-off value for AR expression was > /10% nuclear-stained tumor cells .chisquare test were chosen to determine the differences among variables. Results: AR expression was found in 29.2% (19/65) of TNBCs. Positive expression of AR showed significant correlation with nodal negative disease (p < 0.027). multivariate analysis indicated that AR was a si...

Abstract 1208: Androgen receptor expressing metaplastic carcinoma cell line established from non-caucasian female patient

Abstract Background: Metaplastic carcinoma (MCa) is a rare entity of breast cancer (BCa) where tumor of epithelial origin manifests differentiation into non-glandular, mesenchymal phenotype. These tumors exhibit heterogeneity with spindle, squamous, chondroid or osseous differentiation. Majority of these tumors do not express estrogen or progesterone receptors and are negative for HER-2/neu gene amplification, limiting use of available targeted therapies. This may translate into poor clinical outcome in this subset of patients as opposed to triple negative subtype of breast cancer. Cancer cell lines have been proved to be a valuable tool in understanding pathogenesis of BCa and development of appropriate drugs. Considering tumor heterogeneity, selecting an appropriate cell line model is imperative to understand signaling mechanisms of each of the distinct sub-types of BCa.Aim of this study was to establish and characterize a BCa cell line from a non-caucasian Pakistani patient. Methodology: Cell line was established from primary culture of tumor tissue from a 65 year old Pakistani female patient diagnosed with T4N1M0 MCa of breast. Specimen was procured in Dulbecco's Modified Eagle's Medium and processed under sterile conditions by mincing and gentle pipetting followed by culturing in complete medium supplemented with 10% fetal bovine serum. Epitheliod colonies were visualized after 3 weeks of culture, which were subsequently passaged and propagated. This cell line has been phenotypically and genotypically characterized using karyotyping, gene expression analysis, immunocytochemistry and florescent insitu hybridization (FISH). Results: Cell line has a human karyotype with multiploidy and population doubling time of 60 hours. Gene expression profiling revealed negative expression of ER, PR and positive expression of androgen receptor (AR) and HER-2/neu. FISH analysis was negative for HER-2/neu amplification. Both basal (cytokeratins 5, 14 &amp; 19) and luminal markers (cytokeratin 8 &amp; 18) are expressed at mRNA level along with myoepithelial markers (CD10, S100A7, p-cadherin, desmin, S100A4, S100A2 &amp; α-SMA). In accordance with mesenchymal phenotype, it has low expression of e-cadherin and high expression of vimentin. Invasion assay revealed this cell line to be non-invasive forming spheroids. CAG repeat length of AR is 22 and AR has been found to be functional by luciferase reporter assay in response to treatment with dihydrotestosterone. Conclusions: We report a novel metaplastic carcinoma cell line from a nan-caucasian female patient with functional AR. Targeting AR signaling may be a promising therapeutic target in this rare sub-type of BCa. Citation Format: Nazia Riaz, Zulfiqar Naqvi, Anwar Ali Siddiqui, Shaista Masood Khan, ElNasir Lalani. Androgen receptor expressing metaplastic carcinoma cell line established from non-caucasian female patient. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1208. doi:10.1158/1538-7445.AM2014-1208

Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer.

A subset of triple-negative breast cancer (TNBC) has been reported to express androgen receptor (AR); however, the clinical significance of AR expression in TNBC is unclear. We examined immunohistochemical expression of AR in a large cohort of TNBC cases and correlated its expression with clinicopathologic features and clinical outcome. AR expression was found in 17.7% (87/492) of TNBCs. Positive expression of AR showed significant correlation with older age (p < 0.001), apocrine histology (p = 0.001), and lower histologic grade (p < 0.001). AR was a poor prognostic marker for overall survival (OS) in univariate (p = 0.026) and multivariate (p = 0.008) analyses. In the lymph node-negative (n = 316) subgroup, AR expression was a significant predictor of worse OS and disease-free survival (DFS) in both univariate (p = 0.028 and 0.011) and multivariate (p = 0.024 and 0.01, respectively) analyses. AR expression also was a prognostic factor in pT1 subgroup (OS, p = 0.007; DFS, p = 0.01); however, its prognostic value was not observed in TNBC patients with lymph node metastasis or tumor size larger than pT1. AR-expressing TNBCs represent a distinct breast cancer subgroup with adverse clinical outcome and AR blockade could be a potential endocrine therapy for these TNBC patients. Evaluation of AR status may provide additional information on prognosis and treatment in patients with TNBC.