Paulina Antosik

Assessment of Cyclin D1 Expression: Prognostic Value and Functional Insights in Endometrial Cancer: In Silico Study

Endometrial cancer (EC) is the sixth most common cancer in women worldwide, with rising incidence, particularly in economically developed countries where obesity and type 2 diabetes are prevalent risk factors. EC comprises various histological subtypes with distinct behaviors: Type I tumors are generally estrogen-driven with favorable prognosis, while Type II tumors are hormone-independent, aggressive, and associated with poorer outcomes. Dysregulation of the cell cycle, particularly through cyclin-dependent kinases (CDKs) and their regulators like Cyclin D1 (CCND1), plays a crucial role in EC progression and recurrence. Cyclin D1 overexpression is often observed in the early stages of endometrioid carcinoma and complex hyperplasia, marking potential early carcinogenic events, while lower expression levels are common in high-grade subtypes like serous carcinoma. Although CDK inhibitors targeting Cyclin D1/CDK4/6 complexes have shown therapeutic potential in cancers such as breast and lung, their role in EC remains underexplored. This study integrates immunohistochemical evaluations of Cyclin D1 expression in EC patient samples with data from The Cancer Genome Atlas (TCGA) to assess its prognostic significance across EC subtypes. By correlating molecular, histopathological, and clinical outcomes, we aim to clarify the impact of Cyclin D1 dysregulation on EC progression and recurrence. Our findings may inform more personalized therapeutic approaches, particularly for high-grade and treatment-resistant forms of EC.

Expression of Selected Epithelial‐Mesenchymal Transition Transcription Factors in Endometrial Cancer

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. The aim of this study was to analyze the expression of SNAIL, SLUG, TWIST1, TWIST2, ZEB1, and ZEB 2 in primary tumor and the correlation with morphological and clinical characteristics of EC. The study included 158 patients with EC after surgical treatments: total hysterectomy and lymphadenectomy. The percentages of EC specimens testing positively for the EMT transcription factors were 84.5% for SNAIL, 92.2% for SLUG, 10.9% for TWIST1, 100% for TWIST2, 89% for ZEB1, and 98% for ZEB2. The expression of SLUG in patients with FIGO stage III or IV, type II EC, myometrial invasion ≥ 50% of the uterine wall thickness, and adnexal involvement and in patients with distant metastases was significantly higher. SLUG and ZEB2 expressions were identified as significant predictors of higher FIGO stages (III or IV) on univariate analysis. The overexpression of SLUG was a significant predictor of more aggressive type II EC, myometrial invasion ≥ 50% of the uterine wall thickness, and distant metastases on both univariate and multivariate analysis. Moreover, the overexpression of SLUG and ZEB2 was shown to be significant predictors of adnexal involvement on univariate analysis. ZEB 2 overexpression was identified in multivariate analysis as another independent predictor associated with a lesser likelihood of type II EC. Both univariate and multivariate analyses demonstrated that SLUG expression was the only predictor of 5‐year survival in the study group. The overexpression of SLUG was associated with a significant increase in mortality hazard on univariate analysis and was shown to be a highly significant predictor of death on multivariate analysis. Conclusions. Selected proteins of the EMT pathway play a role in endometrial carcinogenesis; SLUG and ZEB2 expressions in the primary tumor might predict clinical outcomes in EC and drive therapeutic decisions regarding adjuvant treatment in patients with this malignancy.