Progesterone Receptor Immunoreactivity Research Articles

Nandrolone treatment of adolescent female rats alters reproductive tissue and gonadal steroid profile

Anabolic androgenic steroids (AAS) are drugs that mimic the chemical structure of testosterone. The most commonly AAS used by young adults is nandrolone. In the USA, more than 20 % of AAS users started using steroids before the age of 20. This is alarming as most female users are unaware of the detrimental reproductive effects of AAS use such as amenorrhea, anovulation and clitoromegaly. An additional detrimental effect of AAS is their addictive liability. Previous studies indicate that animals self-administer AAS. Furthermore, AAS can cross-sensitize with other drugs of abuse such as cocaine. Our goal was to elucidate the effects of both AAS and cocaine in the reproductive system of female rats. Our hypothesis is that AAS will have a detrimental effect on the reproductive system of female rats. Adolescent female rats were divided into two large groups, one that received nandrolone decanoate (20mg/kg/sc) and another that received sesame oil (vehicle) for 10 successive days starting on day 28. Animals were further subdivided into groups that received saline or cocaine injections (0.01cc/10g) for a total of 4 groups: Oil-Saline, ND-Saline, Oil-Cocaine and ND-Cocaine. One cohort (Day 40) received cocaine or saline injections (0.01cc/10g) from days 40 to 44 and on days 52 and day 62. The other cohort (Day 65) received cocaine or saline injections from days 65 to 69 and on days 77 and 87. Our data show that administration of nandrolone during adolescence increased body weight of female rats. Ovarian weight was decreased, and ovarian tissue presented multiple cysts with fewer follicles. Nandrolone also disrupted uterine morphology. The uterine lumen was increased, the endometrial thickness reduced and thickness of myometrial tissue, as well as uterine weight, was increased. In addition, nandrolone reduced both endometrial estrogen and androgen receptors, an effect lost by day 88. In contrast, uterine tissue at day 63 showed an increase in progesterone receptor (PR) immunoreactivity, whereas PR immunoreactivity decreased in tissue obtained at Day 88 regardless of whether animals had received cocaine. Cocaine also increased PR receptors in uterine tissue at day 63 and 88. Animals treated with nandrolone had higher serum concentrations of testosterone and estradiol and a lower level of progesterone. These data show that nandrolone when administered in supraphysiologic doses during adolescence, has long lasting effects on the reproductive system of the female rat due to the depot effects and long half-life of this drug. These data warrant further research in this area to determine the long-term consequences of early nandrolone exposure on the female reproductive system, as well as fertility. Financial assistance was provided by the Offce of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE-#1545803). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Regression of multiple intracranial meningiomas after cessation of long-term synthetic progesterone (megestrol) medication: case report and autopsy.

We report the history of a woman who developed four intracranial meningiomas during 11 years of therapy with the synthetic progesterone agonist megestrol. After discontinuation of the drug at age 75 years, she improved clinically and a CT scan showed near complete regression of the meningiomas by 78 years. Autopsy was performed at 83 years of age following an accidental death. At the tumor sites, we found both collagenous tissue with small islands of low grade meningioma having strong nuclear immunoreactivity for progesterone receptor and lipomatous tissue. A literature review showed similar cases of radiologic meningioma regression following discontinuance of progestins. Our case is the first one with histopathologic characterization of the end point.

Toker Cell Hyperplasia in the Nipple-Areolar Complex of Transmasculine Individuals

We previously reported breast histopathologic features associated with testosterone therapy in transmasculine chest-contouring surgical specimens. During that study, we observed a high frequency of intraepidermal glands in the nipple-areolar complex (NAC) formed by Toker cells. This study reports Toker cell hyperplasia (TCH)—the presence of clusters of Toker cells consisting of at least 3 contiguous cells and/or glands with lumen formation—in the transmasculine population. Increased numbers of singly dispersed Toker cells were not considered TCH. Among the 444 transmasculine individuals, 82 (18.5%) had a portion of their NAC excised and available for evaluation. We also reviewed the NACs from 55 cisgender women who were aged <50 years old and had full mastectomies. The proportion of transmasculine cases with TCH (20/82; 24.4%) was 1.7-fold higher than cisgender women (8/55; 14.5%) but did not achieve significance (P = .20). However, in cases with TCH, the rate of gland formation is 2.4-fold higher in transmasculine cases, achieving borderline significance (18/82 vs 5/55; P = .06). Among transmasculine individuals, TCH was significantly more likely to be present in those with higher body mass index (P = .03). A subset of 5 transmasculine and 5 cisgender cases were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), cytokeratin 7, and Ki67. All 10 cases were cytokeratin 7+ and Ki67−; 9 out of 10 cases were AR+. Toker cells in transmasculine cases demonstrated variable expression of ER, PR, and HER2. For cisgender cases, Toker cells were consistently ER+, PR−, and HER2−. In conclusion, there is a higher rate of TCH in the transmasculine than cisgender population, particularly among transmasculine individuals with high body mass index and taking testosterone. To our knowledge, this is the first study to demonstrate that Toker cells are AR+. Toker cell features display variable ER, PR, and HER2 immunoreactivity. The clinical significance of TCH in the transmasculine population remains to be elucidated.

Expression of pituitary gonadotropic hormone and sex hormones receptors in endometrial cellular components during menstrual cycle

Introduction. The main function of the endometrium is to create the optimal environment for embryo implantation, controlled by multicomponent signaling pathways. They are modulated by progesterone and estradiol acting through related estrogen receptors (ER) and progesterone receptors (PR). Alteration in steroid hormone, follicle-stimulating hormone (FSHR), and luteinizing hormone (LGHR) receptor expression are underlying factors in the development of various reproductive disorders. Therefore, understanding the physiological features of receptors expression and localization in tissues is extremely important for a proper comprehensive assessment of the endometrial condition.&#x0D; Materials and methods. The expression of ER, PR, FSHR, and LGHR in endometrial samples of healthy females from different menstrual periods, who applied for assisted reproductive technologies (ART) due to male infertility, was assessed by immunofluorescence.&#x0D; Results. The increase in immunoreactivity of ER, PR, FSHR, and LGHR in the glands and stroma of the endometrium is initiated during the early proliferation stage and reaches its maximum during the late proliferation stage. Subsequently, ER expression in the glands and stroma gradually decreases throughout the early and middle stages of secretion; PR immunoreactivity in the stroma and FSHR and LGHR in all endometrial components persists throughout the secretion stage.&#x0D; Conclusion. The correspondence between the change of the studied receptors' expression and endometrium structural features at different stages of the menstrual cycle was demonstrated. The increased expression of ER, PR, FSHR, and LGHR in the endometrium at the proliferation stage coincides with the growth period of the uterine body mucosa, and the increased immunoreactivity of PR, FSHR, and LGHR during the secretion stage is associated with its decidual transformation and seems to create conditions for successful implantation and embryo development if pregnancy occurs.

Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis.

Progesterone resistance including progesterone receptor (PR) deficiency contributes to the pathophysiology of endometriosis; however, whether the PR expression levels in ovarian endometrioma (OE) correlate with the postoperative recurrence of endometriosis remains unclear. This study aimed to investigate the association between PR expression levels in OE and the recurrence of endometriosis. OE specimens were obtained from 132 patients who underwent conservative surgery for endometriosis. The PR expression levels were evaluated using the H score after immunohistochemical staining. Of the 132 patients, 36 (27.3%) experienced recurrence and 96 (72.7%) did not. No differences were observed in the patient characteristics between the recurrence and nonrecurrence groups except for follow-up period. PR immunoreactivity in the epithelial cells (ECs) was statistically significantly lower in the recurrent group than in the nonrecurrent group (P < .01); however, this change was not observed in the stromal cells. Moreover, multivariable logistic regression analysis revealed that the H score of PR in ECs was an independent factor and was statistically significantly associated with the recurrence of endometriosis (P = .01). Furthermore, we divided the patients into PR-negative or PR-positive groups. The cumulative recurrence rate in the negative PR group was statistically significantly higher than that in the positive PR group (P = .046). Low PR expression levels in OE-ECs may predict the recurrence of endometriosis. The PR status in OE-ECs is associated with the pathophysiology of the recurrence of endometriosis, and optimized postoperative management for endometriosis may be provided by referring to the PR status.

TSC2-mutant uterine sarcomas with JAZF1-SUZ12 fusions demonstrate hybrid features of endometrial stromal sarcoma and PEComa and are responsive to mTOR inhibition

Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2 mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12 gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n = 4), LGESS (n = 10), and HGESS (n = 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2 mutations. TSC2 mutations and JAZF1-SUZ12 fusion may help diagnose these tumors and possibly direct effective treatment.

Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma.

When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the differential diagnosis remained challenging after performing immunostaining. Considering the aggressive biological behavior and poor prognosis of uterine MLA, we believe that the accurate recognition of mesonephric-like differentiation (MLD) is important in the diagnosis of endometrial carcinoma. We aimed to investigate the clinicopathological and molecular characteristics of such cases and compared them with those of uterine MLAs. Five patients diagnosed with endometrioid carcinoma (EC) with MLD were included in this study. Histological evaluation, immunostaining, and targeted sequencing were performed. All five tumors showed typical morphological features of MLA, including densely aggregated tubular structures, deep basophilia under low-power magnification microscopy, eosinophilic intraluminal secretions, and diverse growth patterns. Immunostaining revealed moderate-to-strong nuclear immunoreactivity for estrogen and progesterone receptors in more than 50% tumor cells. The staining intensities and proportions of PAX2 and GATA3 were variable. None of the tumors harbored KRAS mutations. Considering the prognostic implications, ancillary tests, including immunostaining and targeted sequencing, should be performed to accurately differentiate between endometrial EC-MLD and uterine MLA.

Angiomyofibroblastoma of the Lower Genital Tract of Women: Report of Two Cases

Superficial angiomyofibroblastoma of the lower genital tract of women is a very rare, benign neoplasm that most commonly arises in the vulvo-vaginal area. Our first case is a 45-year-old woman who presented with menometrorrhagia. On gynecological examination, a pedinculated polipoid mass 2.5 cm in size was found on the cervix. The second case is a 40-year-old woman presented with a nodular mass 5 cm in size on the vulva. She admitted to hospital with itching and cosmetic problems. Histologic examination revealed bland spindled and epithelioid cells arranged around blood vessels. Tumor cells have immunoreactivity for desmin, vimentin, estrogen and progesterone receptors but staining for cytokeratin was negative. In the lipomatous variant, the cells are dispersed into the adipose tissue. Differential diagnosis of lipomatous angiomyofibroblastoma includes; spindle cell lipoma, angiomyolipoma, and cellular angiofibroma. We will discuss the differential diagnosis of these cases with immunohistochemical and morphological findings.

Hepatic Erosion as a Complication of a Peripherally Inserted Central Venous Catheter in a Neonate

Solid Pseudo-papillary neoplasm of the pancreas (SPN) is a rare entity. It represents 0.2-2.7% of all pancreatic cancers. Predominantly occurs in young females in the second to third decades of life. The etiology of SPN involves mutations in the gene that encodes beta-catenin. SPNs are typically indolent tumors, usually confined to the pancreas. We report a case of SPN in a 9-year-old female presented with intermittent abdominal pain for four months. Imaging studies demonstrated a 2.8 cm mass in the tail of the pancreas. The patient underwent a distal pancreatectomy. Pathological evaluation was diagnostic for SPN in the tail of the pancreas. Our case is distinct because of the young age of the patient, peripancreatic soft tissue, perineural, and lymphovascular invasion. The tumor cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin and progesterone receptors

Solid Pseudo-Papillary Neoplasm of Pancreas with Venous Invasion in A 9 Year Old Girl: A Case Report and Literature Review

Solid Pseudo-papillary neoplasm of the pancreas (SPN) is a rare entity. It represents 0.2-2.7% of all pancreatic cancers. Predominantly occurs in young females in the second to third decades of life. The etiology of SPN involves mutations in the gene that encodes beta-catenin. SPNs are typically indolent tumors, usually confined to the pancreas. We report a case of SPN in a 9-year-old female presented with intermittent abdominal pain for four months. Imaging studies demonstrated a 2.8 cm mass in the tail of the pancreas. The patient underwent a distal pancreatectomy. Pathological evaluation was diagnostic for SPN in the tail of the pancreas. Our case is distinct because of the young age of the patient, peripancreatic soft tissue, perineural, and lymphovascular invasion. The tumor cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin and progesterone receptors.

Progesteron receptor expression in insulin producing cells of neuroendocrine neoplasms

Progesterone receptor (PgR) inhibits cell proliferation in pancreatic neuroendocrine neoplasms (PanNEN). In non-neoplastic pancreas, loss of PgR induces β-cell proliferation and insulin production. However, detailed association between PgR and insulin producing PanNENs is poorly understood. Insulin, proinsulin, and PgR were immunolocalized in 82 PanNENs (54 non-functioning PanNENs: NF-PanNENs and 28 insulinomas). The status of immunoreactivity was compared to the clinicopathological factors of the patients. Immunoreactivity was also confirmed by employing the double-immunohistochemistry. These results were also compared with those in non-neoplastic Langerhans islets. PgR immunoreactivity was significantly higher in insulinomas than that in NF-PanNENs (p < 0.001). Insulin and proinsulin immunoreactivity was also detected in 20 (37 %) of (single cell) insulin positive NFs (Inspos-NF-PanNEN), in which PgR expression was higher than in insulin negative NF-PanNENs (Insneg-NF-PanNEN, p = 0.03). The ratio of PgR-insulin double positive cells to overall insulin positive cells, as well as PgR-proinsulin double positive cells to proinsulin positive cells, was detected to the same degree in insulinoma (PgR-insulin 70 %, PgR-proinsulin 66 %), Inspos-NF-PanNENs (PgR-insulin 65 %, PgR-proinsulin 68 %) and normal islet (PgR-insulin 80 %, PgR-proinsulin 72 %). PgR and insulin expressing cells colocalize in tumor cells of the PanNENs regardless of the hormone-related symptoms of the patients. Inhibitory effect of PgR on tumor cells might be associated with the favourable clinical outcome of insulinoma patients.

Bisphenol A (BPA) induces progesterone receptor expression in an estrogen receptor α-dependent manner in perinatal brain

Bisphenol A (BPA) is a xenoestrogen that is prevalent in the environment of industrialized nations due its use in the production of many plastic household items. Virtually all adults in the U.S. have detectable levels of BPA in urine and it can be measured in fetal serum and in breastmilk, making developmental exposure a particular concern. The present study utilizes a progesterone receptor (PR) expression bioassay to assess the estrogen receptor α (ERα)-dependent effects of BPA in fetal rodent brain following maternal exposure. Maternal ingestion of 10 μg/kg/day, but not 50 μg/kg/day, BPA from gestational day 14–22 significantly increased levels of PR immunoreactivity (PRir) in the medial preoptic nucleus (MPN) of female offspring. PR expression in the perinatal MPN is highly dependent on the activation of ERα, but not ERβ, by estrogens. Indeed, injections of BPA (5 μg/kg) to neonates from postnatal day 2–4 (P2–4) significantly increased PR expression in the MPN of postnatal day 5 females compared to the MPN of females administered the oil vehicle. However, pretreatment with the ER antagonist, ICI 182,780 from P1–4 significantly attenuated the effects of BPA on PR expression, indicating an ERα-dependent mechanism. The present results also demonstrate a non-monotonic effect of BPA on the direct expression of a transcription factor in developing brain.

Morphological changes of telocytes in camel efferent ductules in response to seasonal variations during the reproductive cycle

Telocytes (TCs) are a distinct stromal cell type described in many organs. The present study investigated the existence of TCs within the efferent ductules in camel and the changes that occur in their morphology and activity during active and inactive reproductive seasons. TCs in the camel had a cell body and multiple telopodes (TPs), and most TCs had indented nuclei that exhibited prominent intranucleolar chromatin. TCs exhibited seasonal differences which were evaluated by histochemistry, immunohistochemistry (IHC), Transimition electron microscopy (TEM) and scanning electron microscopy (SEM). The presence of TCs in camel efferent ductules has been confirmed by CD34 positive immunostaing. In addition to the expression of the vascular endothelial growth factor (VEGF) which was stronger in the summer season. TCs exhibited stronger immunoreactivity for progesterone and oestrogen alpha receptors (ESR1) in the spring than in the summer. In addition, TCs showed strong positive immunostaining for both vimentin and androgen receptor (AR). Several ultrastructural changes were observed in TCs during the two seasons. TPs in the summer season had delicate ramifications whereas, in the spring, TPs displayed fine arborization and became more corrugated. TCs acquired signs of exaggerated secretory activities in the spring; TPs became expanded and packed with secretory vesicles. Thus, we conclude that, hormonal alterations during the reproductive cycle impact the morphology and secretory behavior of TCs.

Tumor de células de la granulosa extraovárico con mutación FOXL2. Diagnóstico diferencial morfológico e inmunohistoquímico

Extraovarian granulosa cell tumor is a very uncommon tumor and the identification of a recurrent mutation in FOXL2 may be used as another diagnostic tool along with the classical morphological and immunohistochemical findings. Here, we report a new case of extraovarian granulosa cell tumor in a 57 years old female patient presented with a sub-hepatic mass and abdominal pain. Histopathological examination of the excised mass showed features of adult-type granulosa cell tumor with α-inhibin, calretinin, WT1, S100, CD99 and progesterone receptor immunoreactivity. A FOXL2 mutation was detected on molecular biology study. A final diagnosis was an extraovarian adult-type granulosa cell tumor. We discuss the histopathological and immunohistochemical differential diagnosis.

Solid pseudopapillary neoplasms of the pancreas do not express major pancreatic markers in pediatric patients

Solid pseudopapillary neoplasms (SPNs) of the pancreas are classified as "exocrine" pancreatic tumors by the World Health Organization. However, despite numerous studies using immunohistochemistry, electron microscopy, animal models, and molecular biology, the histogenesis of SPN remains unclear. At the same time, our knowledge of human pancreas development has significantly increased. It is now well known that the undifferentiated PDX1+ pancreatic progenitors proliferate and differentiate into endocrine, ductal, and acinar cells, thanks to the expression of numerous transcription factors, which can be used to better characterize pancreatic tumors. In a series of 14 pediatric SPN, we investigated the expression of 4 transcription factors associated with pancreatic development (PDX1, SOX9, PTF1A, and NKX2.2) to obtain new insights into the pathogenesis of SPN. In addition, we tested the expression of different markers of epithelial, endocrine, exocrine, and neural differentiation using both immunohistochemical and immunofluorescence analyses. All tumors displayed the typical histologic features of SPN, with both pseudopapillary and solid patterns. The immunoprofile was characterized by immunoreactivity for β-catenin (100%), progesterone receptor (100%), cyclin D1 (100%), synaptophysin (65%), and S100 (15%). In all cases, tumor cells were negative for the following markers: PDX1, SOX9, PTF1A, NKX2.2, chromogranin A, glucagon, insulin, somatostatin, ghrelin, pancreatic polypeptide, amylase, GFAP, calretinin, EPCAM, and estrogen receptor α. To conclude, SPNs do not express major transcription factors involved in pancreatic development and differentiation, which does not allow for precise pancreatic lineage of tumor cells. Thus, additional studies are still required to determine the origin of SPN.

Investigation of hormone receptor expression and its prognostic value in endometrial stromal sarcoma.

To evaluate the immunohistochemical (IHC) expression of hormone receptors and analyze the prognostic implication of these receptors in patients with endometrial stromal sarcoma (ESS). Fifty-one patients with ESS whose paraffin blocks and pathologic slides, which were obtained after hysterectomy, were available and included in this study. Clinicopathologic data were gathered from patients' medical records, and IHC staining of hormone receptors was performed using tissue microarrays. Estrogen receptor (ER)-alpha was expressed in 37 patients (72.5%), and strong immunoreactivity was observed in 27 patients (52.9%). However, ER-beta expression was observed in only two patients (3.9%). Progesterone receptor (PR) expression was identified in 36 patients (70.6%), and strong immunoreactivity was found in 26 patients (51%). Androgen receptor (AR) expression was observed in 30 patients (58.8%), and strong immunoreactivity was noted in 14 patients (27.5%). Gonadotropin-releasing hormone receptor (GnRH-R) expression was observed in 49 patients (96.1%), but no patient exhibited strong immunoreactivity. All patients expressed CYP19A1, and 43 patients (84.3%) had strong immunoreactivity. ER-alpha, PR, and AR positivity was associated with significantly better overall survival (OS). No patient with AR positivity died of ESS. When the patients were categorized according to ER-alpha, PR, and AR immunoreactivity, triple-positive ESS had the best OS, and triple-negative ESS was linked to the worst OS. Expression of hormone receptors was associated with favorable survival outcome in ESS. Hormone receptors that showed strong expression deserve further evaluation to clarify their importance as a therapeutic target and predictor of treatment response.

Immunohistochemistry in Peritoneal Mesothelioma: A Single-Center Experience of 244 Cases.

- Diagnosis of malignant mesothelioma is more common in the chest than it is in the abdomen. Most published immunohistochemistry data are more applicable to pleural than to peritoneal mesothelioma. - To clarify the practical utility of 17 immunohistochemistry markers in the differential diagnosis of peritoneal mesothelioma with an emphasis on stains for which there is either contradictory information or a paucity of literature. - Consultation files of peritoneal mesothelioma diagnoses rendered from 1999 to 2014 were reviewed; 244 cases were identified. The results of immunohistochemistry markers performed were tabulated. - Immunohistochemistry markers positive in peritoneal mesothelioma in order of sensitivity were calretinin (244 of 244; 100%), WT1 (205 of 218; 94%), CK5/6 (173 of 194; 89%), mesothelin (132 of 150; 88%), and D2-40 (78 of 97; 80%). Markers used to differentiate carcinoma from mesothelioma showed immunoreactivity in peritoneal mesothelioma: estrogen receptor (2 of 84; 2%), B72.3 (6 of 196; 3%), CK20 (5 of 116; 4%), CD15 (7 of 192; 4%), p63 (3 of 62; 5%), carcinoembryonic antigen (9 of 199; 5%), PAX8 (12 of 191; 6%), progesterone receptor (5 of 71; 7%), Ber-EP4 (17 of 209; 8%), and CD138 (9 of 91; 10%). BAP1 loss, increasingly used in the differential diagnosis of benign versus malignant mesothelial proliferation, occured in 55% (99 of 181) of peritoneal mesothelioma cases. - The results support the experience that there is no definitive marker to rule out malignant mesothelioma, including PAX8, estrogen receptor, progesterone receptor, and p63 immunoreactivity. The high rate of immunoreactivity for mesothelin may have a role as a predictive marker for immune targeting. BAP1 loss of 55% in this cohort of peritoneal mesothelioma confirms published observations, and BAP1 retention is seen in a significant proportion of neoplastic cases.

Clinicopathological and molecular characteristics of pediatric meningiomas.

Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Therefore, we analyzed clinical, morphological and molecular profiles of pediatric meningiomas. Forty pediatric meningiomas from January 2002 to June 2015 were studied. 1p36, 14q32 and 22q-deletion were assessed by fluorescent in situ hybridization and mutations of most relevant exons of AKT, SMO, KLF4, TRAF and pTERT using sequencing. Expression of GAB1, stathmin, progesterone receptor (PR), p53 along with MIB-1 LI was examined using immunohistochemistry. There were 36 sporadic and four NF2 associated meningiomas. Among sporadic meningiomas, the majority (72.2%) of cases harbored 22q-deletion. Difference in frequency of combined 1p/14q deletion in Grade-I versus Grade-II/III tumors was not significant (13.7% vs 28.5%, P = 0.57). PR immunoreactivity was seen in 65.5% of Grade-I and 14.2% of Grade-II/III tumors (P = 0.03). The majority (97.2%) of meningiomas were immunonegative for p53. Stathmin and GAB co-expression was observed in 58.3% of cases. Notably, AKT, SMO, KLF4, TRAF7 (exon 17) and pTERT mutations were seen in none of the cases analyzed. 1p/14q codeletion was frequent in skull base as compared to non-skull base meningiomas (23% vs 11.1%, P = 0.37). All NF2 meningiomas harbored 22q-deletion and showed GAB and stathmin co-expression while none showed 1p/14q loss. Pediatric meningiomas share certain phenotypic and cytogenetic characteristics with adult counterparts, but GAB and stathmin co-expression in the majority of cases and non-significant difference in frequency of 1p/14q co-deletion between low- and high-grade meningiomas indicate an inherently aggressive nature. Characteristic AKT/SMO, KLF4/TRAF7 and pTERT genetic alterations seen in adults are distinctly absent in pediatric meningiomas.

Androgen Receptor Expression in Endometrial Stromal Sarcoma: Correlation With Clinicopathologic Features.

Endometrial stromal sarcoma (ESS) is a rare neoplasm comprising only 0.2% to 1% of all uterine malignancies and occurs in women between 42 and 59 yr of age. ESSs frequently express estrogen receptor (ER) and progesterone receptor (PR). However, the published literature contains scant data on the expression and therapeutic/prognostic role of androgen receptor (AR) in ESSs. We undertook this study to characterize the expression of AR along with ER and PR in ESSs and correlate it with clinicopathologic features. The clinical details, slides, and blocks of 25 tumors from 24 patients (September 2010 to February 2016) were retrieved. The diagnosis and grade of ESS were reviewed and immunohistochemistry performed with anti-ER, PR, and AR antibodies. Ages ranged from 18 to 50 yr, with a mean age of 36 yr. Low-grade ESS (LGESS) and high-grade ESS (HGESS) were diagnosed in 15 and 9 patients, respectively. An 18-yr-old woman who initially had LGESS suffered a pelvic recurrence; that exhibited high-grade morphology. Our patients, especially those with HGESS, were much younger compared with published worldwide data. ER, PR, and AR immunoreactivity was observed in 14 (93.3%), 12 (80%), and 11 (73.3%) LGESSs, respectively. This is in contrast to HGESSs, in which 5 (50%) tumors had a triple-negative hormonal profile. AR, like ER and PR, was more frequently expressed in LGESS as compared with HGESS. Whether AR, in addition to ER and PR receptor status, may help guide adjuvant hormonal therapy needs further elucidation.

134 Clinicopathological and Molecular Characteristics of Pediatric Versus Adult Meningiomas

Abstract INTRODUCTION Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Aim of this study was to analyze clinical features, morphological spectrum and molecular profile of adult and pediatric meningiomas METHODS Sixty four adult and forty pediatric meningiomas from January 2002 to June 2015 were assessed for 1p36 14q32 and 22q deletion by FISH and progesterone receptor (PR), p53 along with MIB-1 LI using immunohistochemistry (IHC). Pediaric cases were also assessed for AKT and SMO mutations by sequencing, and expression of GAB1, stathmin, progesterone receptor (PR) by IHC. RESULTS &gt;In the paediatric group, there were 36 sporadic and 4 NF2 associated meningiomas. Amongst sporadic meningiomas, majority (72.2%) of cases harboured 22q deletion. Difference in frequency of combined 1p/14q deletion in Grade I versus Grade II/III tumors was not significant (13.7% vs 28.5%, P = 0.57). PR immunoreactivity was seen in 65.5% of Grade I and 14.2% of Grade II/III tumors (P = 0.03). Majority (97.2%) of meningiomas were immunonegative for p53. GAB and stathmin co-expression was observed in 58.3% of cases. AKT and SMO mutations were seen in none. Frequency of 1p/14q codeletion was higher in skull base tumours as compared to non skull base meningiomas (23% vs 11.1%, p 0.37). All NF2 meningiomas harboured 22q deletion and showed GAB and stathmin co- expression while none showed 1p/14q loss. In adults, deletion of both 1p and 14q were seen in grade II and grade III convexity meningiomas, in 28.5% and 30% of cases, respectively, while it was absent in grade I convexity tumors. Hormone profile of adult cases was similar to pediatric group. CONCLUSION Pediatric meningiomas share phenotypic and genotypic characteristics with adult counterparts, but GAB and stathmin co-expression in majority of cases and no significant difference in frequency of 1p/14q co-deletion between low and high grade meningiomas indicate inherently aggressive nature. SMO and AKT mutations are distinctly absent.