Prognostic role of immunohistochemical and molecular markers in no specific molecular profile endometrial cancer: a systematic review and meta-analysis
No specific molecular profile endometrial cancer represents nearly half of the diagnoses, characterized by substantial molecular heterogeneity and intermediate recurrence and survival outcomes. Currently, no immunohistochemical or molecular markers are established in guidelines to improve prognosis estimation and personalize treatment in no specific molecular profile endometrial cancer. This systematic review and meta-analysis aimed to evaluate the prognostic significance of potential immunohistochemical and molecular surrogate markers in no specific molecular profile endometrial cancers. This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with the International Prospective Register of Systematic Reviews (CRD42024601035). A comprehensive literature search was conducted using Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library (January 1994-December 2024). Studies assessing the prognostic roles of L1 cell adhesion molecule, catenin beta 1, AT-rich interactive domain-containing protein 1A, estrogen receptor, progesterone receptor, and STMN1 expression or mutation status in no specific molecular profile endometrial cancers were included. Methodological quality was assessed using the Newcastle-Ottawa Scale and the Quality in Prognosis Studies tool for risk of bias in prognostic studies. Certainty of evidence for each outcome was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Hazard ratios for recurrence and survival were calculated using random-effects or fixed-effects models depending on heterogeneity. Fourteen retrospective studies including 4654 no specific molecular profile endometrial cancers were analyzed. L1 cell adhesion molecule overexpression significantly predicted higher recurrence (hazard ratio=3.42; 95% confidence interval, 1.86-6.29; P<.001) and worse survival (hazard ratio=4.31; 95% confidence interval, 2.62-7.09; P<.001). Estrogen receptor positivity correlated significantly with reduced recurrence risk (hazard ratio=0.37; 95% confidence interval, 0.26-0.53) and improved survival (hazard ratio=0.22; 95% confidence interval, 0.17-0.29). Loss of progesterone receptor expression was associated with increased recurrence and poorer survival outcomes. Conversely, AT-rich interactive domain-containing protein 1A and catenin beta 1 mutations and STATHMIN1 overexpression did not significantly impact recurrence or survival outcomes. L1 cell adhesion molecule overexpression, estrogen receptor positivity, and progesterone receptor status demonstrate considerable prognostic relevance in no specific molecular profile endometrial cancer, warranting consideration as potential markers for improving patient management, including fertility-sparing approach.