Association of VCP/p97 Expression with Clinicopathological Features and Overall Survival in Endometrioid Endometrial Carcinoma

Background and Aim: Endometrial cancer is considered one of the most common cancers of the female genital system, with endometrioid endometrial carcinoma (EEC) being the most common subtype. Valosin-containing protein (VCP), or p97, acts as an important regulator of cellular protein homeostasis and is thought to play a role in the progression and prognosis of various tumors. This study aimed to evaluate the association of immunohistochemical VCP/p97 expression with clinicopathological features and overall survival in patients with EEC. Methods: This retrospective single-center study utilized hysterectomy specimens obtained from 85 patients diagnosed with EEC between January of 2010 and December of 2022. All cases were retrospectively restaged according to the 2023 FIGO staging system. VCP/p97 expression was evaluated immunohistochemically using a semi-quantitative scoring system based on staining intensity and the percentage of positive tumor cells. Patients with EEC were divided into groups with low and high VCP/p97 expression. Clinicopathological associations, alternative cut-off sensitivity analyses, Kaplan–Meier survival analysis, and Cox regression analyses were performed. Results: Low VCP/p97 expression was detected in 49 cases (57.6%), whereas high expression was detected in 36 cases (42.4%). High VCP/p97 expression was significantly associated with older age, larger tumor size, high FIGO grade, deep myometrial invasion, lymphovascular invasion, cervical and adnexal involvement, pathological lymph node metastasis, distant metastasis, and advanced FIGO stage. Overall survival was significantly worse in the high-expression group (log-rank p < 0.001). In the multivariate Cox regression analysis, high VCP/p97 expression remained associated with poorer overall survival. Conclusions: High immunohistochemical VCP/p97 expression is associated with an adverse clinicopathological phenotype and poorer overall survival in EEC. VCP/p97 may be a considered a candidate tissue-based marker associated with tumor progression features; however, its independent prognostic utility needs to be validated in larger independent cohorts.