Investigating the Factors Associated with the Level of Expression of Estrogen and Progesterone Receptors in Patients Suffering from Colorectal Cancer

Background. The present study was performed to investigate the factors related to the expression level of estrogen and progesterone receptor in patients with colorectal cancer. Material and Methods. This crosssectional study was performed on 54 patients suffering from colorectal cancer referring to Imam Reza Hospital in Birjand during 2018-2019. After the biopsy performed during surgery, the specimen was sent for immunohistochemistry, and the status of receptors was determined. Eventually, the data were analyzed by SPSS 22. Results. Out of the 54 patients studied, 64.8% were male. The mean age of the patients was 62.28 ± 14.03 years. The level of expression of beta-estrogen receptors and progesterone receptors had a significant relationship with age, consuming drugs of abuse, and familial history ( P = 0.001 ). Also, the level of expression of estrogen and progesterone receptors of patients with a more advanced stage of cancer was significantly lower ( P = 0.001 ). Conclusion. The extent of expression of estrogen and progesterone receptors affects the progression and prognosis of disease. Thus, through hormone therapy, a step can be taken to reduce the progression and even to treat colorectal cancer.

Progesterone receptors in AVPV kisspeptin neurons are sufficient for positive feedback induction of the LH surge

Kisspeptin, encoded by Kiss1, stimulates GnRH neurons to govern reproduction. In female rodents, estrogen-sensitive kisspeptin neurons in the rostral anteroventral periventricular (AVPV) hypothalamus are thought to mediate estradiol (E2)-induced positive feedback induction of the preovulatory luteinizing hormone (LH) surge. AVPV kisspeptin neurons co-express estrogen and progesterone receptors (PGR) and are activated during the LH surge. While E2 effects on kisspeptin neurons have been well-studied, progesterone’s regulation of kisspeptin neurons is less understood. Using transgenic mice lacking PGR exclusively in kisspeptin cells (termed KissPRKOs), we previously demonstrated that progesterone action specifically in kisspeptin cells is essential for ovulation and normal fertility. Unlike control females, KissPRKO females did not generate proper LH surges, indicating that PGR signaling in kisspeptin cells is required for proper positive feedback. However, since PGR was knocked out from all kisspeptin neurons in the brain, that study was unable to determine the specific kisspeptin population mediating PGR action on the LH surge. Here, we used targeted Cre-mediated AAV technology to re-introduce PGR selectively into AVPV kisspeptin neurons of adult KissPRKO females, and tested whether this rescues occurrence of the LH surge. We found that targeted upregulation of PGR in kisspeptin neurons exclusively in the AVPV is sufficient to restore proper E2-induced LH surges in KissPRKO females, suggesting that this specific kisspeptin population is a key target of the necessary progesterone action for the surge. These findings further highlight the critical importance of progesterone signaling, along with E2 signaling, in the positive feedback induction of LH surges and ovulation.

Pathologic Characteristics of Pregnancy-Related Meningiomas

Meningiomas are the most common intracranial tumor. During pregnancy, explosive growth of a known meningioma occasionally occurs, but the underlying reasons remain unknown. Prolactin has been suggested as a possible key contributor to pregnancy-related meningioma growth. This study sets out to investigate prolactin and prolactin receptor status in 29 patients with pregnancy-related meningiomas in Denmark, from January 1972 to December 2016, as compared to 68 controls aged 20–45 years, also undergoing resection of a meningioma. Furthermore, we investigated potential differences in the progesterone and estrogen receptor statuses, WHO grade, Ki-67 labeling indices, and locations of the resected meningiomas between the cases and controls. Immunohistochemical analyses were performed, and histopathology and intracranial location were assessed with the investigator blinded for the case–control status. None of the samples stained positive for prolactin and very few samples stained positive for prolactin receptors, equally distributed among cases and controls. Estrogen and progesterone receptors generally followed the same distributional pattern between groups, whereas above cut-point Ki-67 labeling indices for both groups were observed. In conclusion, our results did not support the notion of prolactin as a key contributor to pregnancy-related meningioma growth. Rather, the similarities between the cases and controls suggest that meningiomas early in life may comprise a distinct biological entity.

P–293 Ovarian endometriomas are heterogenous for the steroidogenic function and the expression of estrogen and progesterone receptors

Study question Do all ovarian endometriomas have steroidogenic function and express estrogen and progesterone receptors? Summary answer No, they are heterogenous for the steroidogenic function and the expression of the estrogen and progesterone receptors. What is known already Excessive ectopic estrogen production and up-regulation of estrogen receptor- β, which drives inflammation together with aberrant progesterone signaling leading to impaired decidualization and establishment of ectopic endometrial implants together with down-regulated progesterone receptor (PR) expression are the cardinal molecular features of the disease. However, several fundamental questions still remain to be answered as to whether all ovarian endometriomas carry these molecular aberrations and are steroidogenically active; and if so, the amount of sex steroids they produce correlate with the level of expression of steroidogenic enzymes. We aimed to address these questions in the current study. Study design, size, duration A molecular research study on the surgical specimens collected between April 2020 and December 2020. Seven histopathologically confirmed benign endometriotic cyst capsules obtained from the patients undergoing laparoscopic excision of unilateral ovarian endometriomas without deep infiltrating endometriosis during early follicular phase were used in the study. Participants/materials, setting, methods The mean age±SD (range) of the patients were 32.8±4.9 (30–39). The mean endometrioma size was 5±1.2cm (5–7.5 cm). The samples were cut into equal size pieces of 0.5x0.5cm size and cultured for one day to measure their E2and P4production; and analyzed for the expression of steroidogenic enzymes with quantitative immunoblotting and for the expression of FSH-R, ER and PR with real-time qRT-PCR methods. Luteinized granulosa cells and ovarian cortex were set as references. Main results and the role of chance StAR expression was consistently observed in all samples. However, we noticed significant discrepancies among the samples regarding their steroidogenic function and the expression of aromatase and 3 β-HSD enzymes. E2 production exhibited significant variation (from 5 to 1177pg/mL) from sample to sample despite comparable levels of aromatase expression. ER- βup-regulation as a cardinal molecular feature of endometriosis, was observed in all but one samples (1.46 to 5.48 folds, p < 0.0001). However, its expression level did not correlate with either aromatase expression or the amount of E2 the samples produced. A similar phenomenon was observed in P4 arm of steroidogenesis. Even though 3 β-HSD was expressed by all but one samples detectable amount of P4 was produced only by two samples (up to 15ng/mL). PR expression was down-regulated only in two samples (0.3 to 0.07 folds, p < 0.0001), and significantly up-regulated in the other samples (1.2 to 4.7 folds, p < 0.001). No correlation was found among the samples regarding the expression of PR, 3 β-HSD and P4 output. FSH-R was detected in all samples at the levels comparable to ovarian cortex but its expression level did not show any correlation with ER, aromatase expression and E2 production. Limitations, reasons for caution These results need to be confirmed in studies with larger sample size and different types of endometriotic lesions. Wider implications of the findings: The regulation of steroidogenic activity of endometriomas cannot simply be explained by the expression level of the steroidogenic enzymes, underscoring the importance of other mechanisms that post-translationally regulate their enzymatic activity and metabolism of estrogen and progesterone. PR is not always down-regulated and FSH-R is commonly up-regulated in ovarian endometriomas. Trial registration number Not applicable

Expression of Estrogen Receptor- and Progesterone Receptor-Regulating MicroRNAs in Breast Cancer

In ~70% of breast cancer (BC) cases, estrogen and progesterone receptors (ER and PR) are overexpressed, which can change during tumor progression. Expression changes of these receptors during cancer initiation and progression can be caused by alterations in microRNA (miR, miRNA) expression. To assess the association of BC progression with aberrant expression of miRNAs that target ER and PR mRNAs, we quantified miR-19b, -222, -22, -378a, and -181a in BC samples (n = 174) by real-time PCR. Underexpression of miR-222 and miR-378a in stage T2–T4 BC was characteristic for HER2-overexpressing tumors. In addition, the expression of miR-181a and miR-378a was higher in these tumors than in tumors with a HER2 IHC score of 0 or 1+. In tumors with a Ki-67 index ≥ 14%, all tested miRNAs were underexpressed in BC with a high Allred PR score (6–8). In ER-and-PR–negative tumors, miR-22, miR-222, miR-181a, and miR-378a underexpression was associated with Ki-67 index > 35% (median value). MiR-19b and miR-22 underexpression could be a marker of lymph node metastasis in ER- and/or PR-positive tumors with HER2 IHC score 0. Thus, the association of miR-19b, miR-22, miR-222, miR-378a, and miR-181a levels with BC characteristics is influenced by the status of tumor ER, PR, HER2, and Ki-67.

An Immunohistochemical Study of Estrogen and Progesterone Receptors in Endometrium of Women with Dysfunctional Uterine Bleeding

Abnormal Uterine Bleeding (AUB) is a common complaint that affects large numbers of women from puberty to menopause. It negatively affects health and quality of life of women affected. AUB also has an economic impact for both women and society Abnormal uterine bleeding in premenopausal women is one of the most frequent problems in gynecological practice. Although some of the cases may be due to an organic cause, over 50% of the patients undergoing hysterectomy for menorrhagia have dysfunctional uterine bleeding (DUB). To analyze the percentage and intensity of estrogen receptors (ER) and progesterone receptors (PR) in endometrium of patients with DUB. This study suggests that estrogen and progesterone receptors have an important role in etiopathogenesis of dysfunctional uterine bleeding and alteration in the morphology of endometrium such as development of endometrial hyperplasia. Women in the reproductive age who are complaining of abnormal uterine bleeding, usually have an increase in ER alpha and PR expression in their endometrium.