Immunohistochemical Expression Of Androgen Receptor Research Articles

Immunohistochemical expression of androgen receptors in urothelial carcinoma of urinary bladder. Is it significant? Experience from coastal India.

Bladder carcinoma (BC) ranks second among the genitourinary cancers worldwide. Influence of androgens and expression of androgen receptors in neoplasms are recent findings which were implicated in the development of BC. We aimed to study androgen receptor (AR) expression in bladder urothelial neoplasms and correlate its expression with grade and stage of the tumor. Immunohistochemistry (IHC) was done on samples collected in a tertiary care hospital over one year consisting of 71 urothelial BC and 20 non-neoplastic urothelial conditions. Two pathologists graded the IHC and nuclear staining was considered as positive expression. AR was expressed in 23.9% (17/71) of bladder urothelial neoplasms. AR was expressed in 25.7% and 22.3% of high and low-grade tumors and 25% and 22.3% of non muscle-invasive and muscle-invasive BC. AR expression had no significant correlation with gender, age (> 50 years), muscle invasion or grade. AR expression was significantly absent in non-neoplastic conditions (p = 0.018). AR has varied expression in BC and it is relatively lower in this study population.

Assessment of Immunohistochemical Expression of Androgen Receptor and its Correlation with Histopathological Prognostic Factors in Prostatic Carcinoma

Assessment of Immunohistochemical Expression of Androgen Receptor and its Correlation with Histopathological Prognostic Factors in Prostatic Carcinoma

Androgen Receptor Expression in ER and PR Negative Breast Cancer—A Study from a Tertiary Hospital in Northern India

Objectives Breast cancer is the leading cause of cancer-related deaths in women. Estrogen (ER) and progesterone receptor (PR) status and Her2 overexpression are major determinants in therapeutic decision making. Triple-negative breast cancers (TNBCs) have limited treatment options. Androgen receptor (AR) expression opens up therapeutic avenues for these patients. The aim of this article was to study the immunohistochemical expression of ARs in ER and PR Negative breast carcinomas and to correlate AR expression with various clinical, histopathological, and other immunohistochemical parameters.Materials and Methods It is a cross-sectional study including 105 ER and PR Negative cases of breast carcinoma. Clinical parameters, histopathology, and immunohistochemical expression of AR, Her2, and Ki67 were analyzed in all cases.Results AR expression was observed in 63.8% of ER and PR Negative breast cancers. In this group, AR expression was strongly associated with Her2 co-expression (89.2%) as compared to TNBCs (45.8%); p-value = 0.0002. Significant correlation was also observed between AR expression and tumor necrosis (p-value = 0.034) and postmenopausal status (p = 0.007).Conclusion Our study shows that significant proportion of ER and PR Negative breast carcinomas (ER- PR- Her2+ and TNBCs) show AR expression. We strongly recommend routine evaluation of all hormone receptor-negative breast carcinomas for AR status by immunohistochemistry.

Salivary duct carcinoma- Role of accurate diagnosis for an accurate therapy

Salivary duct carcinoma is an aggressive subtype of primary salivary gland carcinoma with advanced stage at presentation, high rates of metastasis and recurrence. It is most commonly seen in parotid gland of older men with microscopic resemblance to high-grade breast ductal carcinoma. Salivary duct carcinoma mainly affects men over 50 years of age and accounts for 5% to 10% of all salivary gland malignancies. Characteristic histomorphology and immunohistochemical expression of Androgen Receptor (AR) aids the diagnosis of salivary duct carcinoma. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma. Heterologous alterations have been recognized in oncogenes and tumor suppressor genes such as TP53, HRAS, PIK3CA, PTEN, and BRAF as well as AR and HER2. Targeted therapy against these genes may help in broadening treatment options for salivary duct carcinoma. Salivary Duct Carcinoma is one of the most aggressive salivary malignancies with 33% local recurrence and 45% metastasis. We report a case of a 75 years old female patient, who presented with a swelling obliterating the retromandibular groove. FNAC & histopathology confirmed the diagnosis of salivary duct carcinoma.

Immunohistochemical signaling pathways of triple negative and triple positive breast cancers: What is new?

BackgroundBreast cancer (BC) is a heterogeneous disease with different clinically heterogeneous phenotypes. Triple negative BC (TNBC) (ER-/PR-/HER2-) and triple positive BC (TPBC) (ER+/PR+/HER2+) are characterized by unique clinical behavior and therapeutic challenges. However, their exact molecular pathogenesis is not well studied. This study aims to evaluate the immunohistochemical expression of androgen receptor (AR) and c-Myc in TPBCs and TNBCs, correlate their expression with the clinicopathologic features, and assess the correlation between AR and c-Myc expression in TPBCs and TNBCs. Material and methodsAR and c-Myc were immunohistochemically assessed in 45 TNBC and 15 TPBC specimens. ResultsAR expression was detected in 17.7% of TNBC and in all TPBC specimens. c-Myc was expressed in 46.7% of TNBC and in all TPBC specimens. AR and c-Myc expression in TNBC was not associated with any of the clinicopathological features. In TPBC, AR expression was higher in older age, larger size, higher stage, and lymph node metastasis while c-Myc expression was higher in tumors with perineural invasion. This is the first study that reported a significant positive correlation between AR and c-Myc expression in TNBC and TPBC. ConclusionThe current results suggested that AR and c-Myc proteins may contribute to the pathogenesis of TNBC and TPBC. The positive correlation between the two proteins in these subtypes sheds new light on a distinct pathway by which BC cells can modulate their proliferation. Targeting both molecules may provide new therapeutic approaches to improve therapeutic sensitivity and patients' outcomes of these subtypes.

Clinicopathological Characteristics and Androgen Receptor Expression of Triple Negative Breast Cancer: A Retrospective Study in Upper Egypt

Background: Breast cancer is a big challenging problem for public health. Triple negative breast cancer (TNBC) is a subtype of breast cancer which is more aggressive; with no specific treatment guidelines are available. It was noted that androgen receptor (AR) is expressed in TNBC, suggesting that anti-androgens are a promising strategy for treatment. Recently, it was found racial differences in the biologic behavior of TNBC. Objectives: This study aims to assess the clinicopathological features of TNBC in Upper Egypt, and to evaluate the immunohistochemical (IHC) expression of AR in TNBC, in comparison to hormone receptor positive (HR+) invasive duct carcinomas (IDC) as a control group. Patients and Methods: IHC expression of AR was examined in 45 TNBC specimens and 15 HR+ IDC (ER+ and PR+/-). Results: Most of the TNBC cases were ≤50 years and their tumors had high histological grade, presence of lymphovascular emboli, lymph node metastasis and tumor necrosis while few cases revealed duct carcinoma in situ (DCIS) and most patients were stage I & II.TNBC group had significantly younger age, DCIS, higher nodal metastasis and necrosis compared to control group. AR expression was significantly higher in the control group. Conclusion: TNBC occurs at young age and is associated with poor clinicopathological criteria, suggesting the presence of underlying BRCA mutations in our population. AR was expressed in a subset of TNBC, this makes AR an interesting drug target for those patients. Further molecular studies are recommended to uncover pathways of TNBC pathogenesis and improve its therapeutic options.

Role of Sesame Oil in Ameliorating Testicular Damage in a Rat Model of Acute Kidney Injury: A Histological and Immunohistochemical Study

Background: Acute kidney injury (AKI) is characterized by rapid deterioration of renal functions causing many distant organ injuries. Testicular dysfunction was reported upon chronic renal failure, yet little is known about the underlying mechanism of the damaging effect of AKI on testicular structure and function. Sesame oil was proved to have antioxidant effects.Aim of the work: to assess the effects of AKI on the rat testis and the possible protective role of sesame oil.Material and Methods: Twenty-four adult male albino rats were allocated into 4 groups; control, sesame oil-treated (0.5ml/kg orally for 1week), AKI-induced (10mL/kg of 50% glycerol), and AKI-pretreated with sesame oil. Serum testosterone was assayed. Sperms were analyzed. Biochemical assay of tissue malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were performed. Testes specimens were processed for histological staining and immunohistochemical detection of Bcl2, Ki67, and Androgen receptor (AR). Results: AKI group showed a significant decline in serum testosterone, tissue GSH, and SOD with a significant rise in tissue MDA. Sperms revealed a significant rise in abnormal sperm morphology percentage with a significant decline in sperm count. Histological examination depicted various nuclear and cytoplasmic alterations in the testicular histoarchitecture with a significant rise in the collagen fiber deposition. A significant decline in Bcl2, Ki67, and AR immunohistochemical expression were recorded. Sesame oil pretreatment significantly ameliorated all studied parameters.Conclusions: AKI significantly impacted the testicular structure and function through different mechanisms. Sesame oil efficiently ameliorated this adverse effect through its antioxidant, antiapoptotic, antiproliferative, anti-inflammatory, and antifibrotic activities.

Role of pomegranate extract in restoring endometrial androgen receptor expression, proliferation, and pinopodes in a rat model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a multifactorial hormonal disorder accompanied by impairment of endometrial function and structure. Pomegranate is recognized for its role in normalizing the female sex hormones in PCOS with little known about its effect on the accompanying endometrial histological alterations. To assess the possible ameliorative role of pomegranate juice extract (PJE) on endometrial injury in a rat model of PCOS. Forty adult albino rats were equally divided into 4 groups; control, PJE-treated (400mg/kg/day for 3 weeks), letrozole-treated (PCOS) (1mg/kg/day for 3 weeks), and PJE & PCOS groups. Serum Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), testosterone, estradiol, and tissue malondialdehyde (MDA) were assayed. Uterine samples were processed for histological staining with hematoxylin & eosin and Masson's trichrome stains, Ki67 and androgen receptor immunohistochemical staining, and scanning electron microscopy. PCOS group revealed a significant increase in serum FSH, LH, testosterone, estradiol, and tissue MDA. Uterine sections depicted various histological alterations in the endometrium with signs of inflammation. A significant increase in the endometrial collagen fiber content, as well as a significant upregulation in Ki67 and androgen receptor immunohistochemical expression were detected. Scanning electron microscopy showed a significant decrease in the mean number of pinopodes. Concomitant administration of PJE efficiently restored the studied biochemical, histological, and immunohistochemical parameters. PJE ameliorated PCOS accompanying endometrial histological alterations through its antioxidant, anti-inflammatory, anti-fibrotic, anti-proliferative, and anti-androgenic effects most probably due to its polyphenols content.

IMMUNOHISTOCHEMICAL EXPRESSION OF ANDROGEN RECEPTOR IN TRIPLE NEGATIVE BREAST CARCINOMA AT ARMED FORCES INSTITUTE OF PATHOLOGY, RAWALPINDI

Objective: To determine the frequency of immunohistochemical expression of androgen receptor in triplenegative breast carcinoma.
 Study Design: Cross sectional study.
 Duration and Place of Study: This study included 30 cases confirmed as triple negative breast carcinoma atArmed Forces Institute of Pathology Rawalpindi, from Jan to Jul 2018.
 Methodology: Anti-androgen receptor antibody was applied and assessed. Positive expression was defined asgreater and equal to 10% nuclear immunostaining. SPSS-24 was used for analyzing data.
 Results: Out of 30 cases of triple negative breast carcinoma (TNBC), all patients were female. Patients’ agesranged between 21-72 years with a mean age of 46.35 years and a standard deviation of ± 13.4. Androgen receptor expression was positive in 8 cases (27%) of all triple negative breast carcinomas. Out of these androgen receptor (AR) triple negative breast carcinomas; all 8 cases were of histological subtype invasive ductal (mammary) carcinoma, non special type, 7 cases (23%) were of histological grade 3 and 1 was of histological grade 2.
 Conclusion: Androgen receptor expression is observed in 8 cases (27%) of triple negative breast carcinoma cases. Such patients can be selected as candidates for anti- androgen receptor targeted therapy.

Chromosome X aneusomy and androgen receptor gene copy number aberrations in apocrine carcinoma of the breast

Carcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.

Androgen Receptor Immunohistochemical Expression in Undifferentiated/Dedifferentiated Endometrial Carcinoma.

Uterine undifferentiated (UC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They tend to pursue an aggressive clinical course with an advanced stage at presentation. It has been found that androgen receptor (AR) might play a role as a prognostic and therapeutic marker in endometrial carcinoma. However, its expression in UC/DEAC has not been investigated. Herein, the aim of this study was to evaluate the expression of AR along with estrogen receptor (ER), progestin receptor (PR), and HER2 in UC/DEAC and also in other subtypes of high-grade endometrial carcinomas. Review of our pathology database over the period of 2011 to 2019 identified 16 UC/DEAC cases (N=16). We also randomly selected other high-grade endometrial carcinomas including FIGO 3 endometrioid carcinoma (N=9), serous carcinoma (N=8), clear cell carcinoma (N=12) and carcinosarcoma (N=10) for comparison. Immunohistochemical stains for AR, ER, PR, and HER2 were performed on all 55 cases. The protein expression was evaluated both quantitatively and qualitatively. In DEAC cases both the undifferentiated component and the well-differentiated component were recorded separately. Overall, variable degrees of AR reactivity (by Allred scoring method) was present in 63% of UC/DEACs(10/16), 67% of FIGO 3 endometrioid carcinomas (6/9), 88% of serous carcinomas (7/8), 80% of carcinosarcomas (8/10), and 9% of clear cell carcinoma (1/12). AR expression was most often seen with PR (70%) or ER (60%) staining in UC/DEACs. Thirteen cases of UC/DEACs were positive for at least 1 hormone receptor. HER2 was negative in all UC/DEACs. Almost all other high-grade carcinoma cases were negative for HER2 except 20% of carcinosarcoma (2/10) and 13% of serous carcinoma (1/8) which showed 3+ HER2. Loss of AR appears to be associated with worse clinicopathologic parameters in UC/DEAC. AR is highly expressed in UC/DEAC, and in the majority of FIGO 3 endometrioid carcinomas, serous carcinomas, and carcinosarcoma. These findings suggest a potential role for androgen inhibitors in the management of patients with these tumors.

Implications of androgen receptor and FUS expression on tumor progression in urothelial carcinoma.

To examine the immunohistochemical expression of AR and FUS in urothelial carcinoma in relation to prognostic parameters and to extrapolate any possible link between the expression of both markers and tumor progression. Retrospective study using immunohistochemical staining for AR and FUS on (88) cases of urothelial carcinoma. AR shows statistically significant relations with late tumor stage, high tumor grade, and non-papillary tumor pattern. On the other hand, FUS expression correlates with early tumor stage, low tumor grade and papillary pattern. An inverse relation is found between AR and FUS expression (p=0.001). Cases with high AR IHC expression show statistically significant shorter OS, RFS and PFS compared to cases with low AR expression. Cases with high FUS IHC expression reveal statistically significant longer OS, RFS and PFS compared to cases with low FUS expression. FUS expression is associated with favorable prognostic parameters of UC. A possible interaction is suggested between FUS and AR pathways involved in urothelial cancer progression. Manipulating FUS levels and androgen deprivation therapy can provide new promising targets for treatment trials.

Lack of Androgen Receptor Expression Selects for Basal-Like Phenotype and Is a Predictor of Poor Clinical Outcome in Non-Metastatic Triple Negative Breast Cancer.

Background: Androgen receptor (AR) has emerged as a significant favorable prognostic indicator in estrogen receptor expressing (ER+) breast cancer (BCa); however, its clinical and biological relevance in triple negative breast cancer (TNBC) and association with cancer stem cell (CSC) markers remain ambiguous.Methods: We examined the immunohistochemical expression of AR in a cohort of stage I–III TNBC cases (n = 197) with a long-term clinical follow-up data (mean follow-up = 53.6 months). Significance of AR expression was correlated with prognostic biomarkers including cancer stem cell markers (CD44, CD24, and ALDH1), basal markers (CK5, CK14, and nestin), proliferation marker (ki-67), apoptotic marker (Bcl-2), and COX-2. Expression of CK5 and nestin was used for the categorization of TNBC into basal (TN, CK5+, and/or nestin+) and non-basal (TN, CK5−, and/or nestin−) phenotypes, and Kaplan–Meier curves were used for estimation of overall survival and breast cancer-specific survival (BCSS).Results: AR expression was observed in 18.8% of non-metastatic TNBC tumors. Expression of AR correlated with lower grade (P < 0.001) and conferred a favorable prognostic significance in patients with axillary lymph node metastasis (P = 0.005). Lack of AR expression correlated with expression of CSC phenotype (CD44+/CD24−) (P < 0.001), COX-2 (P = 0.02), basal markers (CK5: P = 0.03), and nestin (P = 0.01). Basal-like phenotype (TN, CK5+, and/or nestin+) correlated with quadruple-negative breast cancer (QNBC) and showed a significant association with adverse prognostic markers including high proliferation index (P < 0.001), expression of COX-2 (P = 0.009), and CSC phenotype (CD44+/CD24−: P = 0.01). Expression of AR remained an independent prognostic indicator for improved overall survival (P = 0.003), whereas basal-like phenotype was associated with an adverse BCSS (P = 0.013).Conclusions: Assessment of AR and basal markers identified biologically and clinically distinct subgroups of TNBC. Expression of AR defined a low-risk TNBC subgroup associated with improved overall survival, whereas expression of basal markers (CK5 and nestin) identified a high-risk subgroup associated with adverse BCSS. Integration of immunohistochemical analysis of AR and basal biomarkers to the assessment of TNBC tumors is expected to improve the prognostication of an otherwise heterogeneous disease.

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment.

Salivary duct carcinoma (SDC) is an aggressive subtype of primary salivary gland carcinoma, often with an advanced stage at presentation and high rates of metastasis and recurrence. It most commonly arises in the parotid gland of older men and microscopically resembles high-grade breast ductal carcinoma. While 50years have lapsed since the first report of this entity, recent intensive studies have shed light on its biologic, genetic, and clinical characteristics. The diagnosis of SDC is aided by the immunohistochemical expression of androgen receptor (AR) coupled with its characteristic histomorphology. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma, and ancillary studies using cell block material can facilitate the specific diagnosis of SDC. In surgical specimens, certain histologic features are important prognostic factors, including nuclear pleomorphism, mitotic counts, vascular invasion, and the morphology at the invasion front. Several clinical studies have shown promising results using targeted therapy for AR and human epidermal growth factor receptor 2 (HER2), and the latest version of the National Comprehensive Cancer Network guidelines recommends the evaluation of AR and HER2 status before treatment. Recent molecular analyses have revealed multiple heterogeneous alterations in well-known oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF. Clinical trials of drugs targeting these genes may broaden the treatment options for SDC in the near future.

Androgen Receptor: Evaluation and Correlation with Recurrence and Clinicopathological Parameters in Papillary Urothelial Carcinomas of the Urinary Bladder.

Papillary urothelial carcinoma (PUC) is the most common malignant tumor of the urinary bladder. Urothelial tumors are notorious for frequent recurrences and follow a chronic relapsing course in most of the patients. In Pakistan, the incidence of PUC is showing a rising trend. Various immunohistochemical (IHC) markers including androgens have been studied as prognostic and predictive markers in PUC with conflicting results. Androgen is a steroid-based sex hormone and plays an important role in different body organs such as urinary bladder, prostate, muscles, and brain. We aimed to investigate the role of the IHC expression of androgen receptor (AR) as a predictor of recurrence in papillary urothelial carcinoma patients. Eighty-four patients were included in the study. Tissues from the biopsy specimens of these cases were stained with antibodies against AR; 17% of the cases demonstrated a positive AR IHC expression. The expression was slightly more common in low-grade carcinoma. The AR expression was not significantly associated with clinicopathological features. Recurrence was observed in 49% of the cases, and it was significantly more common in AR-negative cases (p-value: 0.025). Eighteen out of 19 patients who died of disease were AR- negative, but no statistical significance was observed. We conclude that the IHC expression of AR can be used as a predictive marker for PUC as it correlates with the recurrence rate.

Immunohistochemical expression of androgen receptors in prostate carcinoma and benign prostatic hyperplasia

Background/Aim. Prostate carcinoma (PCa) and its parent organ are influenced by hormones, which is used for therapeutic purposes. Through androgen receptors (AR) androgens influence cell growth and function, proliferation, differentiation, apoptosis, lipid metabolism and secretory activity of the prostate, as well as development and progression of PCa. An antiandrogen therapy is carried out in patients with metastatic PCa, in order to block effects of androgens. By conducting immunohistochemical analysis of androgen receptors in the PCa tissue, we can assume how the tumour will react to an administered antiandrogen therapy, both in androgen-positive and androgen-negative, resistant tumours. Knowledge of the presence of AR in the tumour tissue may serve as a prognostic indicator in histopathological analysis. The aim of this study was to evaluate the expression of AR in patients with benign prostatic hyperplasia (BPH) and in those with PCa, before therapy. Methods. Immunohistochemical analysis was carried out by using anti-human AR monoclonal antibody AR441 (DAKO), and presence and intensity of AR were semi-quantitatively evaluated in 195 patients, 165 with BPH and 30 with PCa. Material for analysis was obtained by needle biopsy or transurethral resection of the prostate (TURP). Results. All secretory cells in patients with BPH were intensively androgen positive, while in patients with PCa they were mostly moderately to highly positive, but with foci of negativity. The observed negative correlation between AR and Gleason score and the International Society of Urologic Pathology (ISUP) grade group of PCa was not statistically significant. Conclusion. Study results indicate that PCa, before therapy, is androgen-dependent, with a high level of AR expression.

Immunohistochemical Expression of Androgen Receptor (AR) and its Relationship with Clinicpathological Parameters in Breast Cancer

Immunohistochemical Expression of Androgen Receptor (AR) and its Relationship with Clinicpathological Parameters in Breast Cancer

Immunohistochemical Expression of Androgen Receptors (AR) in Various Breast Cancer Subtypes.

BACKGROUND:Breast carcinoma ranks the first among malignant tumours in females and is the chief cause of cancer-related mortality. Androgen in implicated in the induction of proliferation and growth of mammary cells through binding to their corresponding receptors. Androgens influence the risk of acquiring breast cancer through either direct binding to androgen receptors (AR) or indirectly through their transformation to estradiol or competing for steroid binding proteins.AIM:To study the expression of AR in various breast cancer subtypes and to elucidate its clinical significance by correlating it with clinicopathological parameters.METHODS:One hundred and fifty breast cancer cases were studied using AR immunohistochemistry, and its expression was correlated with different clinicopathologic parameters and with ER, PR, Her-2/neu and Ki 67 expression.RESULTS:AR was expressed in 91 breast carcinoma cases out of 150 examined. There was a statistically significant correlation between AR expression and tumour size, mitotic count, tumour necrosis, infiltrative borders, the hormonal status of the tumour and subsequently luminal subtypes (p < 0.05). A subset of studied TNBC (34.6%) also expressed AR. On the other hand, there was no significant correlation between AR expression and other clinicopathological parameters.CONCLUSION:Positive AR immunostaining was associated with favourable prognostic factors and luminal subtypes (A&B). Also, a subset of TNBC cases showed positive AR expression. These results introduce the current potent, next-generation AR- antagonist as possible target therapy in breast cancer. Further researches on AR expression in breast cancer are recommended on a larger scale with follow up and survival to validate the current results.

Prognostic Significance of High Androgen Receptor Expression in Prostatic Acinar Adenocarcinoma

Background:Quantitative immunohistochemical expression of Androgen receptor (AR) has not been evaluated as a prognostic biomarker of prostate cancer in our population, therefore in the current study we aimed to evaluate the association of AR expression in prostatic acinar adenocarcinoma with various prognostic parameters like tumor quantification, Gleason score, WHO grade group and perineural invasion.Methods:Total 121 cases of biopsy proven prostatic acinar adenocarcinoma were selected from records of pathology department archives from January 2013 till December 2017. Hematoxylin and eosin stained slides and paraffin blocks were retrieved and new sections were cut where necessary. Slides of all cases were reviewed by two senior histopathologists and pathologic characteristics like Gleason score, WHO grade, tumor quantification, perineural and lymphovascular invasion were evaluated. Androgen receptor immunohistochemistry was applied on all cases.Results:Low AR expression was noted in 53 cases (43.8%) while high AR expression was seen in 68 cases (56.2%). Significant association of AR expression was noted with total Gleason score, WHO grade and percentage of tissue involvement (tumor quantification). Univariate binary logistic regression showed patients with low Gleason scores (scores 6,7 or 8) and low WHO grade (grade 1, 2 or 3) were less likely to express high AR expression in comparison to high Gleason score (score 9) and high WHO grade group (grade 5) respectively. Similarly, cases with low tissue involvement by carcinoma (<50%) were less likely to show high AR expression in comparison to cases with >50% tissue involvement by carcinoma.Conclusion:Significant association of AR expression was noted with total Gleason score, WHO grade and percentage of tissue involvement (tumor quantification) which are among the most important markers of tumor progression; therefore we suggest that AR expression should be performed in patients with prostatic adenocarcinoma for prognostic stratification of the patients.

Clinicopathologic Study of Endometrial and Hormonal Changes after Metformin Therapy in Patients with Polycystic Ovary Syndrome

Background: polycystic ovary syndrome (PCOS) is a common disorder of women in reproductive age. PCOS, a complex genetic condition, is a heterogeneous syndrome of clinical and/or biochemical androgen excess, ovulatory dysfunction and polycystic ovaries. Metformin has been shown to improve fertility in the ovulatory patients with PCOS, inducing not only a high ovulation and pregnancy rate, but also reducing the incidence of miscarriages. Aim of the Work: this study aimed to evaluate the effects of metformin on hormonal profile and endometrial tissue, including pattern of immunohistochemical expression of androgen receptors (AR), in patients with PCOS. Patients and Methods: 50 women with polycystic ovary syndrome (PCOS) were enrolled in this study. Each patient was submitted to detailed history taking, clinical examination including hair all over the body, body weight, body height and body mass index (BMI), transvaginal sonography, laboratory investigations ( LH, FSH, fasting insulin, free testosterone). Endometrial samples were taken for histopathological evaluation and assessment of androgen receptors. These investigations were done before and after three months of metformin treatment. Results: there was a significant decrease of BMI of the studied cases after metformin administration (P value <0.001). Also, there was a significant decrease of LH level after metformin administration from 8.07 ± 2.48 mIU/ml to 6.85 ± 3.5 mIU/ml and a significant decrease of fasting insulin level from 13.5 ± 5.3 before metformin administration to 10.2 ± 6.9 after administration. As regard to pathological results before metformin treatment, histopathological examination of the endometrial specimens revealed features of early proliferative endometrium in 32 cases, late proliferative in 10 cases, while the remaining 8 cases showed features of simple endometrial hyperplasia. Among the 32 cases with early proliferative endometrium, 30 cases progressed to late proliferative endometrium after treatment with metformin, while the remaining 2 cases showed no morphologic changes. Among the 10 cases with late proliferative endometrium, 3 cases progressed to early secretory phase, 3 cases to mid-secretory and 4 cases progressed to late secretory endometrium indicative of ovulation. Regression of hyperplasia was noted in 3 out of the 8 cases diagnosed as simple endometrial hyperplasia. As regard to immunohistochemistry (IHC), we found that women with PCOS exhibited marked increase in endometrial androgen receptors (AR) expression compared to the normal fertile controls (p<0.001). Significant decrease in AR expression in endometrial tissue after metformin therapy was observed (p<0.003). Conclusion: metformin therapy in patients with PCOS restores menstrual cyclicity, induces ovulation and showing decrease in LH level, fasting insulin, and AR expression in endometrial tissue.