Rare forms of endometrial cancer: Growth factor levels in tumor tissue and patient serum.

Abstract

e17623 Background: The pathogenesis of uterine serous carcinoma (USC) and clear cell carcinoma (CCC) is not well understood. Investigating growth factors is crucial for understanding the mechanisms behind their aggressive behavior. The aim of this study was to evaluate the levels of TGFβ1, EGF, and EGFR in tumor tissue and serum of patients with different histological types of endometrial cancer. Methods: The study included 21 patients with USC and 20 with CCC. The comparison group consisted of 20 patients with grade 3 endometrioid endometrial carcinoma (EEC). The diagnosis was morphologically verified and confirmed by postoperative histological examination. The mean patient age was 59 ± 6.8 years. Levels of EGF, EGFR, and TGFβ1 were determined by enzyme-linked immunosorbent assay (ELISA) in tumor tissue homogenates and serum samples. Control samples included intact endometrium (from 20 patients with uterine fibroids) and serum from healthy women (n=20). All patients provided written informed consent. Statistical analysis was performed using parametric and nonparametric tests with correction for multiple comparisons. Results: EEC was characterized by a 1.3- to 2.1-fold increase in EGF, EGFR, and TGFβ1 levels in tumor tissue and serum compared with controls. In USC and CCC tumor samples, TGFβ1 and EGF levels were significantly lower (1.8- to 4.2-fold) than in EEC tumors, while EGFR concentration showed no significant differences. Furthermore, EGF and TGFβ1 levels in CCC and USC tumors were 1.6- to 2.2-fold lower compared with intact endometrium. In contrast, serum levels of the studied growth factors in patients with rare endometrial carcinomas exceeded control values by 2.1- to 3.1-fold but did not differ significantly from levels in EEC patients, with the exception of EGF, the concentration of which was on average 1.5-fold higher. Conclusions: USC and CCC are distinguished from EEC by low levels of EGF and TGFβ1 in tumor tissue but elevated concentrations of EGF in the blood, which may be associated with the activation of alternative signaling pathways. USC and CCC likely actively produce and release EGF into the bloodstream, a process linked to the inflammatory response that stimulates angiogenesis and metastasis. The identified growth factor profiles may contribute to the aggressiveness of rare endometrial carcinomas and explain their resistance to therapy.