Modern concepts of endometrial squamous cell carcinoma.

Abstract

e17626 Background: Endometrial cancer is the leading oncogynecological malignancy, with a concerning trend of shifting age incidence and worsening prognosis. Over 75% of endometrial carcinomas are represented by estrogen-dependent endometrioid adenocarcinoma (EAC). The remaining 20% comprise more aggressive rare tumors, including squamous cell carcinoma of the endometrium (SCCE). Morphologically, EAC with squamous metaplasia (found in 15% of cases) is distinguished from pure SCCE (reported in about 2%). The etiology and pathogenesis of these carcinomas are insufficiently understood. This study aimed to define the pathomorphological features of EAC with squamous metaplasia and SCCE by analyzing the association between immunohistochemical and virological factors. Methods: The study was conducted on retrospective material from 90 patients (aged 32–89 years) with verified diagnoses of EAC, EAC with squamous metaplasia, and SCCE. All patients received standard treatment. Morphological structure, expression of p16 and pRb markers, and detection of high-risk HPV DNA (types 16 and 18) were analyzed in resected tumor tissues. Comparative and statistical analysis was performed using the Mann-Whitney U test. Results: All patients with SCCE were in deep menopause; the tumor developed against a background of atrophic endometrium and was accompanied by diffuse adenomyosis in 82% of cases. SCCE was characterized by low differentiation grade (G3) in 75% of patients, whereas G3 was found in only 38% of EAC with squamous metaplasia. Markers p16 and pRb demonstrated signs of progression from EAC to SCCE. The median p16 expression level was 1.7-fold higher in squamous metaplasia (p=0.059) and 2.3-fold higher in SCCE (p=0.020) compared to pure EAC. The median pRb levels showed almost no differences in the carcinoma groups; however, in the SCCE group, a sharp 2.3-fold decrease in pRb expression was observed (p=0.041). Altered p16 and pRb expression is closely linked to the E6 protein, which determines the malignant phenotype of HPV infection. HPV was detected in 46.7% of EAC cases, 52.9% of EAC with squamous metaplasia, and 78.5% of SCCE cases. Typing analysis revealed that HPV type 18 was more frequent in EAC with squamous metaplasia (66.7%), whereas HPV type 16 predominated in SCCE (82%). Furthermore, the level of the E6 protein in tissue with a squamous component was 37.4 times higher than in intact (tumor-free) endometrium. Conclusions: The obtained data reveal the potential role of p16, pRb markers, and HPV in the etiology of endometrial squamous cell carcinoma and open prospects for targeted therapy.