Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140–125.606, P=0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

Objectives: Deubiquitinating enzymes have been increasingly implicated in tumor progression and metastasis. Ubiquitin-specific protease 17 (USP17) and translationally controlled tumor protein 1 (TPT1) are associated with cell proliferation, migration, and cancer progression; however, their differential expression in matched primary and metastatic tissues of high-grade serous ovarian carcinoma (HGSC) has not been well defined. This study aimed to compare USP17 and TPT1 expression between matched primary and metastatic HGSC tissues and to explore their association with metastatic disease. Methods: This retrospective study included 33 patients diagnosed with HGSC. Immunohistochemical analysis of USP17 and TPT1 expression was performed using tissue microarrays (TMA) constructed from matched primary ovarian tumor tissues and corresponding metastatic tissues. USP17 expression was evaluated using a semi-quantitative composite immunohistochemical scoring system, while TPT1 expression was assessed using a semi-quantitative immunoreactivity index. Paired statistical analyses were applied to compare expression patterns between primary and metastatic tissues. Results: Primary and metastatic USP17 expression levels showed a positive correlation (Spearman’s rho = 0.349, p = 0.047) whereas paired comparison showed no significant difference between the two sites (p = 0.438). In contrast, TPT1 expression showed no statistically significant correlation (Spearman’s rho = 0.285, p = 0.107) or paired comparison showed no difference (p = 0.107) between matched primary and metastatic tissues. USP17 and TPT1 expression levels were significantly positively correlated in both primary (Spearman’s rho = 0.406, p = 0.019) and matched metastatic tissues (Spearman’s rho = 0.351, p = 0.045). Neither USP17 nor TPT1 expression showed a significant association with International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node involvement, or receipt of neoadjuvant chemotherapy (NACT). Conclusions: These findings indicate a positive correlation between USP17 expression in paired primary and metastatic HGSC tissues without significant changes in overall expression levels, though causality cannot be inferred. Conversely, TPT1 expression showed no significant correlation or site-specific variation between matched tumor tissues. Further prospective and functional studies are required to validate these findings and clarify their biological significance.