Uterine serous and clear cell carcinomas: Hormonal profile and expression of steroid hormone receptors in mitochondria.

Abstract

e17624 Background: Uterine serous carcinoma (USC) and clear cell carcinoma (CCC) are rare but aggressive histological subtypes of endometrial cancer associated with a poor prognosis. Beyond their classical role in energy metabolism, mitochondria are involved in cell signaling. Steroid hormone receptors are localized within mitochondria, allowing estrogens, progesterone, and androgens to directly influence mitochondrial function, thereby regulating apoptosis and energy metabolism. The aim of this study was a comparative assessment of steroid hormone levels and their receptor expression in mitochondria isolated from USC and CCC tissues versus mitochondria from intact endometrium. Methods: Mitochondria were isolated from tumor tissues of 41 patients with rare forms of endometrial cancer: USC (n=21) and CCC (n=20). All patients presented with stage III–IV, high-grade (G3) disease; the mean age was 59.6±6.7 years. Mitochondria from histologically normal (intact) endometrium (n=20) obtained from women undergoing surgery for uterine fibroids (mean age 57.8±8.2 years) served as controls. Concentrations of estrone (E1), estradiol (E2), estriol (E3), testosterone (T), progesterone (P4), and receptors (ERα, ERβ, AR, PR) were determined in the purified mitochondrial fraction using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using parametric and nonparametric tests with adjustments for multiple comparisons. Results: In USC and CCC mitochondria, a statistically significant (p < 0.05) increase was observed compared to the control group for: E2 (1.3- to 2-fold), E3 (1.8- to 2.2-fold), P4 and T (1.5-fold on average), ERβ (more than 2-fold), and PR (3.4- to 5.2-fold). However, ERα and AR levels were significantly increased only in USC (1.8-fold, p < 0.05 and 2.2-fold, p < 0.05, respectively), whereas no significant differences were found in CCC mitochondria. Conclusions: The findings demonstrate significant alterations in the mitochondrial hormonal and receptor profiles in serous and clear cell endometrial carcinomas. Overexpression of ERβ and PR, alongside the accumulation of steroid hormones, indicates the activation of mitochondrial hormonal signaling pathways. The observed differences suggest distinct mechanisms of hormonal regulation: estrogen- and androgen-dependent signaling predominates in USC, while progesterone-dependent signaling predominates in CCC. These features may determine differences in the biological behavior of these tumors and their response to therapy.