Androgen Receptor Immunoreactivity Research Articles

Intraductal carcinomas of the salivary glands: a clinicopathological and molecular genetic analysis of twenty-seven cases

Objective: To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands. Methods: Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People's Hospital and two cases from Department of Pathology, Henan Provincial People's Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed. Results: There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption. Conclusions: IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.

The opioid peptide β-endorphin interferes with the pituitary-testis axis in the Mozambique tilapia Oreochromis mossambicus.

Although the involvement of β-endorphin (β-ERP) in vertebrate reproduction has been suggested, its role in testicular activity is not clear in fish. We describe the influence of β-ERP on spermatogenesis in a cichlid fish in the present paper. In comparison to the control group, the administration of β-ERP (3µg) caused a significant increase in the number of spermatogonia-A and spermatids. Following treatment with β-ERP (6µg), a significant increase in the number of spermatogonia-A was observed, whereas the numbers of all the other germ cells, excluding spermatogonia-B, significantly decreased in comparison to those in the control group. In addition, treatment of fish with 6µg β-ERP resulted in a significant reduction in the dimensions of the lumen and seminiferous lobules, the level of immunopositive androgen receptor (AR) expression in Sertoli cells, and the percentage of luteinizing hormone (LH) immunolabeled in the pituitary compared to those in the control group or the group treated with 3µg β-ERP. In contrast, the intensity of AR immunoreactivity and the percentage of LH immunolabeling were substantially increased in fish treated with 3µg β-ERP compared to those in thecontrol group. These findings reveal for the first time that a low dose of β-ERP stimulates the recruitment of spermatogonia as well as spermateleosis, whereas a high concentration affects the recruitment of germ cells prior to meiotic division in tilapia. These results suggest that β-ERP exerts modulatory effects at the testicular and hypophysial levels through alterations in AR expression and LH secretory activity, respectively, in teleosts.

Chronic Starvation-Induced Alterations in Biochemical Parameters and Hypothalamic-Pituitary-Testicular Axis in the Mozambique Tilapia Oreochromis mossambicus (Cichlidae)

Although fish are often exposed to food restrictions in natural or aquafarming conditions, the relationship between altered energy status and the reproduction is not well understood. The aim of the present investigation was to elucidate the effect of chronic food-deprivation on energy status and reproductive axis in male Mozambique tilapia Oreochromis mossambicus. The controls received food ad libitum, whereas the fish in the starvation group were deprived of food for 21 days. The liver showed significantly higher levels of gluconeogenesis and triglycerides, whereas the levels of blood glucose and total protein content in the liver were significantly lower in starved fish compared to controls. Furthermore, the mean numbers of different spermatogenic cells, such as spermatogonia-A, primary spermatocytes, secondary spermatocytes, early spermatids, and late spermatids were significantly lower, but the number of spermatogonia-B did not show a significant difference compared to controls. In starved fish, there was a significant increase in germ cell apoptosis at different stages of development concomitant with faintly immunoreactive androgen receptors in the Sertoli cells of the testis compared with controls. In addition, the percent areas of gonadotropin-releasing hormone—immunoreactive fibres and luteinizing hormone—immunoreactive content—in the proximal pars distalis part of the pituitary gland were significantly lower in starved fish compared with controls. Collectively, these results suggest that decreased energy status negatively affects the gonadotropin-releasing hormone—luteinizing hormone – testicular axis, leading to inhibition of spermatogenesis before entry of germ cells into meiosis through increased apoptosis and decreased expression of androgen receptors in the testis of the Mozambique tilapia.

Histamine H2 receptor agonist dimaprit dihydrochloride stimulates the hypothalamo-hypophysial-testicular axis in the cichlid fish Oreochromis mossambicus

Histamine is a naturally occurring biogenic monoamine that acts at both central and peripheral levels, serving a crucial role in regulating a range of physiological processes in vertebrates, including immune function and reproduction. This research aims to understand whether the histamine H2 receptor agonist dimaprit dihydrochloride (DIMP) affects the hypothalamo-hypophysial-testis (HPT) axis of the Mozambique tilapia. Treatment with 5 μg DIMP did not alter the numbers of spermatogonia-B and secondary spermatocytes, but caused a significant increase in the numbers of other germ cells. However, treatment with 20 μg DIMP resulted in significantly higher numbers of all germ cells, including spermatogonia-A and B, primary and secondary spermatocytes, and early and late spermatids, compared to those of controls or 5 μg DIMP-treated fish. There was a dose-dependent increase in the diameters of seminiferous lobules and lumens, but the diameter of the interstitium was significantly decreased in DIMP-treated fish. Furthermore, there was also a dose-dependent, significant increase in the density of gonadotropin-releasing hormone-immunoreactive fibres and intensity of androgen receptor immunoreactivity in 5 and 20 μg DIMP-treated fish, concomitant with a significant increase in serum levels of luteinizing hormone in 5 or 20 μg DIMP-treated fish compared to those of controls. Collectively, these results, for the first time, suggest that treatment with DIMP exerts a stimulatory effect on the HPT axis in the teleosts.

Effects of postnatal exposure to cadmium on male sexual incentive motivation and copulatory behavior: Estrogen and androgen receptors expression in adult brain rat

There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1–56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -β), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.

Ocular and extraocular sebaceous carcinomas: A retrospective study with emphasis on the presence of insitu lesion and discussion and review of the histogenesis of extraocular sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare carcinoma classified as ocular or extraocular. Ocular SC is believed to arise from the meibomian glands or the glands of Zeis. However, the origin of extraocular SC is controversial because there is no evidence of carcinoma arising from pre-existing sebaceous glands. Several hypotheses about the origin of extraocular SC have been proposed, including one suggesting an origin from intraepidermal neoplastic cells. Although extraocular SCs have been shown to occasionally comprise intraepidermal neoplastic cells, no study has investigated whether intraepidermal neoplastic cells possess sebaceous differentiation. The present study analyzed the clinicopathological features of ocular and extraocular SC, with an emphasis on the presence of in situ (intraepithelial) lesions. It retrospectively reviewed the clinicopathological features of eight patients with ocular and three patients with extraocular SC (eight women and three men; median age, 72 years), respectively. In situ (intraepithelial) lesions were observed in four of the eight ocular SC cases and one of the three extraocular SC cases and an apocrine component was noted in one patient with ocular SC (seboapocrine carcinoma). In addition, immunohistochemical analyses showed that the androgen receptor (AR) was expressed in all ocular SCs and two of the three extraocular SC cases. Adipophilin expression was observed in all ocular and extraocular SC. In situ lesions of extraocular SC showed positive immunoreactivity for both AR and adipophilin. The present study is the first to demonstrate sebaceous differentiation in in situ lesions of extraocular SC. The possible origin of extraocular SC is speculated to be the progenitor cells present in the sebaceous duct or interfollicular epidermis. The results of the present study and reported cases of SC in situ indicate that extraocular SC also arises from intraepidermal neoplastic cells.

Androgen receptors in the forebrain: A study in adult male cats.

Androgens and their receptors are present throughout the body. Various structures such as muscles, genitals, and prostate express androgen receptors. The central nervous system also expresses androgen receptors. Androgens cross the blood-brain barrier to reach these central areas. In the central nervous system, androgens are involved in multiple functions. The current study investigated in which forebrain areas androgens are expressed in the male cat. Androgen receptor immunoreactive (AR-IR) nuclei were plotted and the results were quantified with a Heidelberg Topaz II + scanner and Linocolor 5.0 software. The density and intensity of the labeled cells were the main outcomes of interest. The analysis revealed a dense distribution of AR-IR nuclei in the preoptic area, periventricular complex of the hypothalamus, posterior hypothalamic area, ventromedial hypothalamic, parvocellular hypothalamic, infundibular, and supramammillary nucleus. Numerous AR-IR cells were also observed in the dorsal division of the anterior olfactory nucleus, lateral septal nucleus, medial and lateral divisions of the bed nucleus of the stria terminalis, lateral olfactory tract nucleus, anterior amygdaloid area, and the central and medial amygdaloid nuclei. AR-IR nuclei were predominantly observed in areas involved in autonomic and neuroendocrinergic responses which are important for many physiological processes and behaviors.

Seasonal changes of the prostate gland in the raccoon (Procyon lotor) inhabiting Hokkaido, Japan.

In the prostate gland of the raccoon (Procyon lotor), the morphological appearance of the epithelial cells, such as basal and luminal cells, and the expressions of p63, androgen receptor (AR), and proliferating cell nuclear antigen (PCNA) were examined histologically and immunohistochemically to clarify their seasonal dynamics throughout the year. In this study, the regression with luminal cell defluxion and the regeneration process of the prostatic glandular epithelium was revealed in the seasons with declined spermatogenesis (June to August). The expression of p63 was observed only in the basal cells. AR immunoreactivity in the luminal cells was shown in the developed and regenerating (close to developed) prostates, whereas the basal cells exhibited AR immunoreactivity all year round. PCNA expression was rare in epithelial cells of the developed prostate gland. In the regressed gland, the basal cells demonstrated proliferative ability, whereas PCNA of the luminal cells appeared for the first time in the regenerating phase. This study is the first to clarify the regression with luminal cell defluxion and restoration and the seasonal dynamics of AR expression and proliferative activity in the prostate gland of seasonal breeders.

Androgen receptors immunoreactivity in the rat brain of males with same-sex preference

Androgen receptors (AR) are crucial in the control of male sexual behavior and sex preference. AR are particularly concentrated in areas related with the neuroendocrine control of sex preference including the medial amygdala (MeA), the ventromedial nucleus of the hypothalamus (VMH), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA), the nucleus accumbens (Acb), the suprachiasmatic (SCh) and supraoptic (SO) nuclei, but also seem to be important for the control of reproductive processes in the hippocampus (CA1-CA4 and dentate gyrus, DG). In the present study we analyzed the density of AR in these brain areas of adult male rats with sexual preference (established in a three-compartment box). Same-sex preference was produced in male rats by the prenatal administration of the aromatase inhibitor, letrozole (0.56 μg/kg/ml s.c. G10-22) that usually produces 1–2 animals per litter with same sex preference, while the others retain a female sex preference. We also included a group of proestrus females that had a clear preference for a sexually active male. AR were analyzed by immunocytochemistry using PG21 as primary antibody. We also measured total plasma testosterone concentrations by radioimmunoassay. In males with same sex preference there was a specific AR overexpression in CA3 and CA4 that suggests a feminized pattern because females in proestrus trend to show a higher density of AR in these hippocampal areas. Sex differences in AR density were found in the anterior cingulate cortex (ACg) and frontoparietal cortex (FrPa). Serum levels of testosterone did not differ between groups. Data are discussed based on the role of AR in the hippocampus.

Chronic exposure to aquacultural stressors affects pituitary-testis axis in the Mozambique tilapia Oreochromis mossambicus.

Reproduction in fish is modulated by several factors that include environmental and endocrine components. The aim of this study was to elucidate the effect of aquacultural stressors along the pituitary-testis axis in a continuously breeding cichlid fish Oreochromis mossambicus. The fish (35.05 ± 2.20g) were divided into three groups (n = 10 in each group, n = 5 in each replicate), namely initial controls (euthanized on the day of initiation of experiment), time-matched controls (kept undisturbed), and stressed fish, which were subjected to different kinds of randomized aquacultural stressors such as handling, chasing, frequent netting, and low water levels, daily for a period of 21days. Although the gonadosomatic index and the mean numbers of spermatogonia-A and spermatogonia-B did not differ significantly among different experimental groups, significant decrease was observed in the mean numbers of primary spermatocytes, secondary spermatocytes, early spermatids, and late spermatids in fish exposed to stressors compared to those of initial controls and time-matched controls. While the diameter of the seminiferous lobule was significantly lower, the size of the lumen and the serum levels of cortisol were significantly increased in stressed fish compared with initial controls and time-matched controls. Furthermore, weak androgen receptor immunoreactivity was observed in the Sertoli cells of the testis in contrast to the strongly immunoreactive androgen receptors in initial controls and time-matched controls. Concomitant with this, there was a significant decrease in the percent area and the intensity of luteinizing hormone (LH) immunoreactive content in the proximal pars distalis (PPD) region of the pituitary gland in stressed fish compared with initial controls and time-matched controls. Overall, these results suggest that exposure to chronic aquacultural stressors causes suppression of LH synthesis in the pituitary gland concomitant with decreased androgen receptor expression and blockade of recruitment of germline cells at the meiosis stage. This inhibition appears to be mediated through the hypothalamic-pituitary-interrenal axis in the tilapia O. mossambicus.

Effect of androgens on Sertoli cell maturation in human testis from birth to puberty

BackgroundAndrogens are well known to be necessary for spermatogenesis. The purpose of this study was to determine Sertoli cell responsiveness to androgens according to age from birth to puberty.ResultsTesticular tissue samples were studied in a population of 84 control boys classified into seven groups according to age: group 1 (1–30 days), group 2 (1–3 months), group 3 (3–6 months), group 4 (0.5–3 years), group 5 (3–6 years), group 6 (6–12 years), and group 7 (12–16 years). We compared these data with those of 2 situations of pathology linked to androgens: 1/premature secretion of testosterone: 4 cases of Leydig cell tumor (LCT) in childhood; and 2 /defect of androgen receptors (AR): 4 cases of complete form of insensitivity to androgen syndrome (CAIS). In control boys, AR immunoreactivity (ir) in Sertoli cells appeared between 4.6 and 10.8 years of age, Anti-Mullerian Hormone (AMH) ir in Sertoli cells disappeared between 9.2 and 10.2 years of age. Connexin 43 (Cx43) ir in Sertoli cells and histological features of the onset of spermatogenesis appeared between 10.8 and 13,8 years of age. Cx43 ir was significantly higher in 12–16 year-olds than in younger boys. In case of CAIS, no spermatogenesis was observed, both AR and Cx43 ir were undetectable and AMH ir was elevated in Sertoli cells even at pubertal age. In the vicinity of LCTs, spermatogenesis occurred and both AR and Cx43 ir were strongly positive and AMH ir in Sertoli cells was low for age.ConclusionsAndrogen action on Sertoli cells is required for onset of spermatogenesis and premature androgen secretion by LCT can induce spermatogenesis in the vicinity of the tumor. AR ir appeared earlier than onset of spermatogenesis, with large interindividual variability. The timing and mechanisms of Sertoli cell responsiveness to androgens are important issues for understanding the induction of spermatogenesis at puberty.

Subacute exposure to aluminum chloride causes prolonged morphological insults in the ventral male prostate and in the female prostate of adult gerbils.

Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl3 ) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl3 (10mg/kg) for 30 consecutive days. The animals were euthanized 1day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate.

Paternal and infanticidal behavior in the Mongolian gerbil (Meriones unguiculatus): An approach to neuroendocrine regulation

This study aimed to provide evidence on estrogen and androgen pathways regulating the Mongolian gerbil's paternal and infanticidal behaviors (Meriones unguiculatus). We analyzed estrogen receptor alpha (ERα) and androgen receptor (AR) distribution in the medial preoptic area (mPOA), the bed nucleus of stria terminalis (BNST), as well as the anterior hypothalamic nucleus (AHN), the ventromedial hypothalamus nucleus (VMH), and the periaqueductal gray area (PAG) nuclei activated when males interact paternally or aggressively with the pups, respectively. Twenty aggressive males towards the pups and 10 paternal were selected through a screen paternal behavior test. Three groups of 10 males each were formed: paternal males (PAT), males with testosterone (T)-induced paternal behavior (T-PAT), and aggressive males (AGG). Male gerbils could interact with a pup for a few minutes, and their brains were removed and dissected for ERα and AR immunoreactivity (ir). The results showed that in T-PAT and PAT males, the number of ERα-ir and AR-ir cells in the mPOA/BNST was significantly higher than in AGG males. In AGG males, the number of ERα-ir and AR-ir cells in the AHN/VMH/PAG was significantly higher than PAT and T-PAT males. This difference in the presence of ERα and AR in nuclei activated in paternal interactions in the Mongolian gerbil supports the idea that these receptors participate in regulating paternal behavior. Also, these results suggest, for the first time, that they could be involved in the infanticidal behavior in this rodent.

Simultaneous expression of steroid sulfatase and androgen receptor reduced overall survival of patients with epithelial ovarian tumors

BackgroundOvarian cancer is usually diagnosed at an advanced stage due to its early asymptomatic course and late-stage non-specific symptoms. This highlights the importance of researching the molecular mechanisms involved in ovarian carcinogenesis as well as the discovery of novel prognostic markers that could help improve the survival outcome of patients. The aim of this study was to evaluate the expression of the steroid sulfatase (STS) in 154 samples of primary ovarian tumors. This protein is crucial in the intracellular conversion of sulfated steroid hormones to active steroid hormones. The presence of STS, 3β-HSD, and 17β-HSD1 result in the production of testosterone which act through the androgen receptor (AR) in the tumor cell. The presence of STS and AR in epithelial ovarian tumors and their association to the overall survival of patients was evaluated using Kaplan–Meier and Cox regression analyses.ResultsImmunoreactivity for STS was detected in 65% of the tumors and no association was observed with histological subtypes and clinical stages of the tumor. The STS expression in the tumors exhibiting immunoreactive AR resulted in a reduced survival (log-rank test, p = 0.032) and a risk factor in univariate and multivariate analysis, HR = 3.46, CI95% 1.00–11.92, p = 0.049 and HR = 5.92, CI95% 1.34–26.09, p = 0.019, respectively.ConclusionsThese findings suggest that the intracellular synthesis of testosterone acting through its receptor can promote tumor growth and progression. Moreover, the simultaneous expression of STS and AR constitutes an independent predictor of poor prognosis in epithelial ovarian tumors.

Morphometric analysis and redox state of the testicles in nandrolone decanoate and swimming treated adult male rats

BackgroundDuring the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH).ResultsDiameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control.ConclusionsNandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

Androgen receptors in areas of the spinal cord and brainstem: A study in adult male cats.

Sex hormones, including androgens and estrogens, play an important role in autonomic, reproductive and sexual behavior. The areas that are important in these behaviors lie within the spinal cord and brainstem. Relevant dysfunctional behavior in patients with altered androgen availability or androgen receptor sensitivity might be explained by the distribution of androgens and their receptors in the central nervous system. We hypothesize that autonomic dysfunction is correlated with the androgen sensitivity of spinal cord and brainstem areas responsible for autonomic functions. In this study, androgen receptor immunoreactive (AR‐IR) nuclei in the spinal cord and brainstem were studied using the androgen receptor antibody PG21 in four uncastrated young adult male cats. A dense distribution of AR‐IR nuclei was detected in the superior layers of the dorsal horn, including lamina I. Intensely stained nuclei, but less densely distributed, were found in lamina X and preganglionic sympathetic and parasympathetic cells of the intermediolateral cell column. Areas in the caudal brainstem showing a high density of AR‐IR nuclei included the area postrema, the dorsal motor vagus nucleus and the retrotrapezoid nucleus. More cranially, the central linear nucleus in the pons contained a dense distribution of AR‐IR nuclei. The mesencephalic periaqueductal gray (PAG) showed a dense distribution of AR‐IR nuclei apart from the most central part of the PAG directly adjacent to the ependymal lining. Other areas in the mesencephalon with a dense distribution of AR‐IR nuclei were the dorsal raphe nucleus, the retrorubral nucleus, the substantia nigra and the ventral tegmental area of Tsai. It is concluded that AR‐IR nuclei are located in specific areas of the central nervous system that are involved in the control of sensory function and autonomic behavior. Furthermore, damage of these AR‐IR areas might explain related dysfunction in humans.

Prognostic Value of Androgen Receptor in Triple Negative Breast Cancer of Iranian Patients in Yazd Region

Background: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients.Methods: In this study a total of 60 TNBC patients treated between 2011 - 2016 in Shahid Sadoughi and Mortaz Hospital were included and their medical records were analyze. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with ?10% nuclear staining were considered AR-positive, while the ones with <10% staining were considered AR-negative. The association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC was analyzed. Results: The result showed that AR expression in TBNC correlated with high risk of recurrence but no significant correlation with the age, grade, tumor size, lymph node status, type of diagnosis, tumor location, and Ki-67 level was observed. Positive immunoreactivity for AR was observed in 19 out of 60 (11%) specimens. No correlation was observed between the AR expression and the age, grade, tumor size, lymph node status, type of diagnosis, tumor location, and Ki-67 level. The AR-positive patients exhibited high risk of recurrence (P=0.016) and death (P=0.015) in comparison with the AR-negative patients. Concusions: AR may not be a suitable biomarker and treatment target for the Iranian Yazd patients with TNBC.

The Modulatory Role of Vitamin C in Boldenone Undecylenate Induced Testicular Oxidative Damage and Androgen Receptor Dysregulation in Adult Male Rats.

Background: This study explored the effect of vitamin C (Vit-C) administration on the reproductive function of adult male Wistar rats injected with boldenone undecylenate (BOL). Methods: Rats were randomly assigned into control, vehicle control, Vit-C (120 mg/kg b.wt./day, orally), BOL (received 5 mg/kg b.wt./week, IM) and BOL+Vit-C-treated groups. After eight weeks, hormonal assay, semen evaluation, testicular enzymes, and antioxidants biomarkers were assessed. Besides, the histopathological and immunohistochemical investigations of the androgen receptor (AR) expression were performed. Results: The results revealed that serum testosterone, acid phosphatase, sorbitol dehydrogenase, sperm abnormalities, and testicular malondialdehyde were significantly incremented in the BOL-treated group. Testicular weight, sperm count, and sperm motility together with serum levels of luteinizing hormone, follicle-stimulating hormone, and estradiol, and testicular testosterone, catalase, superoxide dismutase, and reduced glutathione showed a significant decrease following BOL treatment. Besides, the AR immunoreactivity was significantly decreased in testicular tissues. Vit-C co-administration with BOL significantly relieved the BOL-induced sperm abnormalities, reduced sperm motility, testicular enzyme leakage, and oxidative damage. However, Vit-C could rescue neither BOL-induced hormonal disturbances nor AR down-regulation. Conclusions: The results provide further insight into the mechanisms of BOL-induced reproductive dysfunction and its partial recovery by Vit-C.

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<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<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<0.001) and longer survival. A positive AR expression was associated with a positive IGF-1R expression (p<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.

Abstract P6-05-07: Comparison of androgen receptor expression in core needle biopsies with surgical samples in primary breast cancer

Abstract Background Breast cancer subtypes are important for the prognosis and optimal treatment of breast cancer patients. Moreover, these subtypes are determined by immunohistochemistry (IHC) using ER, PgR, HER2 and Ki-67 expressions in practical medicine. The androgen receptor (AR) is frequently expressed in breast cancer but has not yet been standardized. IHC is the standard procedure when using preoperative biopsy specimens to determine biomarker expressions. In this study, the differences in AR expression between core needle biopsy (CNB) and matched surgical samples were examined and the relationship between AR expression and the clinicopathological factors was investigated. Patients and Methods Primary breast cancer patients (n=432) who underwent surgery between March 2017 and June 2019 were diagnosed pathologically using CNB. The biomarker expression of 220 of the patients were determined using surgical samples without preoperative treatment. The AR expression was evaluated using IHC and the expression was divided into the negative, low (<10%) and high (≥10%) groups. The H-score (staining intensity x percentage of positive cells) was used to compare the extent of nuclear immunoreactivity for AR between CNB and the matched surgical samples in 119 CNB cases with an AR ≥ 10%. Breast cancer subtypes were categorized using the IHC data derived from ER/PgR, HER2 and Ki-67 (cutoff: 20%) values. Results 1. The AR positive rates was 57.5%(low: 10%; high: 47.5%)in all primary cases. AR expression significantly correlated with positive ER/PgR, lower Ki-67 values and nuclear grade, negative p53 and HER2. The AR expression rate was 73.4% in Luminal A, 59.3% in Luminal B, 65.2% in Luminal HER2, 43.3% in HER2 enriched and 22.2% in triple negative cases. 2. The AR positive rates of the matched cases were 65.0% in CNB cases (low: 10.9%; high: 54.1%) and 44.5% (low: 8.8%; high: 35.9%) in surgical sample cases (p<0.0001). However, there was no significant difference between AR expression and ER, PgR and HER2 status. Ki-67 index values were higher in the surgical samples (median: 35.0%) than CNB samples (median: 27.0%). 3. The median H-score was 130.0 (mean+/- SD: 143.2+/-63.0%) in CNB samples and 85.0 (mean+/-SD: 94.8+/-59.5%) in the surgical samples (p<0.0001), respectively. Conclusion A discordance in the AR expression and H-score between the core needle biopsies and matched surgical samples was found. These findings suggest that a fixation condition may affect the expression status after resection of samples. AR expression using IHC should be evaluated in core needle biopsies. However, further studies are needed for clinical use. Citation Format: Nobuyuki Arima, Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue. Comparison of androgen receptor expression in core needle biopsies with surgical samples in primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-05-07.