No abstract

Carcinosarcomas (CSs) are composed of two separate histological components and are rare neoplasms of the female genital tract. Therefore, CS pathogenesis has not yet been fully elucidated. In the present study, immunohistochemical techniques were used to determine the role of p53 and Ki-67 overexpression in female genital tract CSs. The study group was comprised of 36 patients with CSs originating from the uterus (n=31), cervix (n=3) and ovary (n=2), as well as 3 metastatic tissues. p53 was overexpressed in the epithelial component of 23 out of 36 (64%) tumors, and in the mesenchymal component of 20 out of 36 (56%) tumors. In both CS components, there was a significant correlation between p53 overexpression and patient age and ovarian metastases. Ki-67 overexpression was detected in the epithelial component in 15 out of 36 (42%) cases, and in the mesenchymal component in 13 out of 36 (36%) neoplasms. There was a significant correlation of p53 overexpression between the carcinomatous and sarcomatous components (R=0.884, P<0.001). A significant correlation was also found in Ki-67 immunoreactivity between the two CS components (R=0.676, P<0.001). However, p53 overexpression was not correlated with Ki-67 immunostaining in both tumor components. In conclusion, based on immunohistochemical results, p53 was overexpressed in more than half of the female genital tract CSs included in the present study, either at the epithelial or mesenchymal component. The correlation between p53 or Ki-67 overexpression in both tumor components supports the combination theory of histogenesis in the majority of these tumors.

In the scientific literature, a selected number of reports have investigated the impact of proliferative activity on the development and progression of uterine carcinosarcomas (UC). The aim of the present retrospective study was to compare the immunohistochemical proliferation markers [Ki67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 3 (MCM3), and topoisomerase IIα (topoIIα)] assessment in both components of UC. A total of 30 paraffin-embedded slides of UCs, obtained from patients who underwent surgery between January 1, 2006, and December 31, 2020, were analyzed. Medical records and clinicopathological data of patients were reviewed. Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki67, PCNA, MCM3 and topoIIα. Ki67-positive nuclear immunoreactivity was reported in 20 (67%) and 16 (53%) UC carcinomatous and sarcomatous components, respectively. In the epithelial component, Ki67 positive staining was related to the International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.025), and histological grade (G1 vs. G2/G3, P=0.031). Nuclear PCNA reactivity was observed in 18 (60%) and 16 (53%) carcinomatous and sarcomatous components, respectively. Notably, all four cases with omental metastases were PCNA-positive, and a relationship between staining pattern and the existence of metastases was of significant value (P= 0.018). MCM3-positive nuclear staining was found nearly twice as high in the carcinomatous (n=19; 63%), compared with the sarcomatous (n=11; 37%) component, respectively, and MCM3 expression in the epithelial component was related to clinical stage (P=0.030), and the existence of omental metastasis (P=0.012). In addition, out of the 30 UCs, 17 (57%) and 13 (43%) showed topoIIα positivity in the carcinomatous and sarcomatous UC components, respectively. A significant relationship between protein immunoreactivity and FIGO stage (P=0.049), and omental metastasis (P=0.026) was revealed to exist. However, no significant differences between expression of proliferation markers and clinicopathological features in the sarcomatous UC component were identified. Finally, a significant correlation between each protein immunohistochemical staining was demonstrated, particularly in the sarcomatous UC component. Collectively, a combined analysis of Ki67, PCNA, MCM3, and topoIIα may provide more detailed information of cell-cycle alterations determining the heterogeneity of uterine carcinosarcomas.