Emanuela Marcenaro

The role of the Androgen Receptor (AR) in endometrial cancer aggressiveness: Correlation with other prognostic markers and therapeutic implications. A retrospective observational study

Endometrial carcinoma (EC) is the most common gynecological malignancy, with increasing incidence linked to rising risk factors. This retrospective observational study investigates the role of the Androgen Receptor (AR) in EC aggressiveness, its correlation with other prognostic markers, and its potential therapeutic implications. A total of 143 cases of EC treated with hysterectomy were analyzed for AR expression and its association with clinicopathological and molecular markers, including estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, β-catenin, E-cadherin, Bcl-2, Cyclin D1, and mismatch repair (MMR) status. AR expression was significantly higher in low-grade endometrioid carcinoma (LGEC) compared to high-grade endometrioid carcinoma (HGEC) and other high-risk histologies (p = 0.015), suggesting a role in less aggressive tumor phenotypes. AR strongly correlated with ER and PR (p < 0.0001), indicating shared regulatory pathways. A borderline association with tumor-infiltrating lymphocytes (TILs) suggests a potential role in immune response. However, AR expression did not significantly correlate with markers of proliferation (Ki-67) or tumor suppression (p53), nor with β-catenin, E-cadherin, Bcl-2, Cyclin D1, or MMR status. These findings support AR as a prognostic marker in hormone-responsive EC subtypes and suggest that AR-targeted therapies could be beneficial, particularly in ER/PR-negative tumors. The study highlights the potential integration of AR status into molecular profiling, aiding in personalized treatment strategies for improved patient outcomes in EC management.

Natural killer cell impairment in ovarian clear cell carcinoma

Abstract In the present study, we report the analysis of NK cells derived from patients suffering from a rare ovarian cancer histotype of clear cell carcinoma (OCCC) resistant to conventional chemotherapies. We analyzed the phenotype of NK cells derived from peripheral blood (PB) and peritoneal fluid (PF) and evaluated cytotoxic interactions between NK cells and autologous tumor cells (ATC) derived from patients. We provided evidence of impaired degranulation capacity of NK cells derived from patients’ PF in the presence of ATC. Analyzing tumor cell ligands recognized by NK cell receptors, we found that ATC are characterized by an HLA class I+ phenotype (although the level of HLA-I expression varies among all patients) and by a heterogeneous expression of ligands for activating NK receptors (from normal to decreased expression of some markers). Furthermore, we observed a down-regulation of crucial NK cell activating receptors, primarily DNAX Accessory Molecule-1 (DNAM-1), on tumor-associated NK cells. Based on these results, we propose that this severe lysis defect may be due to both negative interactions between HLA-I-specific inhibitory NK cell receptors/HLA-I molecules and to defective interactions between activating NK receptors and cognate ligands. In conclusion, for the first time, the phenotypic and functional properties of tumor-associated NK cells and their ATC derived from PF of patients with advanced stage of OCCC were characterized. Taken together results indicate altered interactions between NK cells and ATC and shed light on the aggressive mechanisms of this cancer histotype. Further studies on this rare tumor will be helpful to improve and define more effective therapies.