Kisspeptin and GPR54 Receptor Expression in Endometrial Cancer Tissue.

Kisspeptin (KISS) is a natural peptide-discovered in 1996 as a factor inhibiting the ability to metastasize in malignant melanoma. This protein plays also a regulatory role in the process of puberty, the menstrual cycle, spermatogenesis, implantation and development of the human placenta. The present study aimed to evaluate the expression of KISS and its receptor GPR54 in endometrial cancer (EC) tissue, depending on the histological type of cancer, its stage, various demographic characteristics, and clinical conditions in 214 hysterectomy patients. Expression of KISS and GPR54 was confirmed in 99.5% and 100% of the cases, respectively. Hormone replacement therapy and the coexistence of the anti-Müllerian type 2 receptor in cancer tissue enhanced KISS expression. Smoking, on the other hand, decreased KISS expression. GPR54 expression increased with the advancement of the disease (according to FIGO classification). Also, the presence of the anti-Müllerian type 2 receptor in EC increased the level of GPR54. Hypertension, age and miscarriage harmed the presence of GPR54. The histological type of cancer, diabetes type 2, body mass index, hormonal contraception, number of deliveries, birth weight of newborns, breastfeeding time, and the presence of AMH in EC tissue were not associated with the expression of either KISS nor GPR54. The KISS level was also significantly related to the GPR54 level. Considering that KISS is a non-toxic peptide with antimetastatic properties, further investigation is essential to determine the clinical significance of this peptide.

Anti-Müllerian Hormone Type II Receptor Expression in Endometrial Cancer Tissue.

Anti-Müllerian hormone (AMH) is responsible for the Müllerian ducts' regression in male fetuses. In cells of cancers with AMH receptors (AMHRII), AMH induces cell cycle arrest or apoptosis. As AMH occurs naturally and does not exhibit significant side effects while reducing neoplastic cell colonies, it can be considered as a potential therapeutic agent for cancer treatment. The purpose of this study was to assess the AMHRII expression in endometrial cancer (EC) in correlation to various demographic data and clinical conditions. Immunohistochemical analysis was used to assess AMHRII expression in EC tissue samples retrieved from 230 women with pre-cancerous state of endometrium (PCS) and EC. AMHRII was detected in 100% of samples. No statistical difference was observed for AMHRII expression depending on the histopathological type of EC, cancer staging, body mass index, and age, as well as the number of years of menstruation, births and miscarriages, and average and total breastfeeding time. Diabetes mellitus type 2 is the only factor that has an impact on AMHRII expression in EC tissue. Thus, this study supports the idea of theoretical use of AMH in EC treatment because all histopathological types of EC at all stages of advancement present receptors for AMH.

Anti-Müllerian Hormone Expression in Endometrial Cancer Tissue.

Anti-Müllerian hormone (AMH) is a commonly known factor secreted by Sertoli cells, responsible for regression of the Müllerian ducts in male fetuses. AMH has also other functions in humans. In vivo and in vitro studies have shown that AMH inhibits cell cycle and induces apoptosis in cancers with AMH receptors. The aim of the study was to assess whether the tissue of pre-cancerous states of endometrium (PCS) and various histopathologic types of endometrial cancer (EC) exhibit the presence of AMH. We aimed to investigate whether the potential presence of the protein concerns menopausal women or those regularly menstruating, and whether is related to cancers with a good or a bad prognosis, as well as what other factors may influence AMH expression. The undertaken analysis was carried out on tissues retrieved from 232 women who underwent surgical treatment for PCS and EC. Tissues were prepared for immunohistochemical assessment with the use of a tissue microarrays method. AMH expression was confirmed in 23 patients with well differentiated endometrioid adenocarcinoma (G1), moderately differentiated endometrioid adenocarcinoma (G2), clear cell carcinoma (CCA) and nonatypical hyperplasia. AMH was not found in EC tissues in regularly menstruating women. An appropriately long mean period of breastfeeding in line with a prolonged period of hormonal activity had a positive effect on AMH expression. Our results may suggest that AMH is a factor which protects the organism against cancer, and should be further investigated as a potential prognosis marker and a therapeutic agent.