Tumor Budding in Gynecologic Cancer as a Marker for Poor Survival: A Systematic Review and Meta-Analysis of the Perspectives of Epithelial–Mesenchymal Transition

SIMPLE SUMMARY: Tumor budding (TB) is an emerging prognostic marker in various cancers; specifically, its role is well established in colorectal cancer. There are very few studies on TB’s role in gynecological cancers. Thus, we studied tumor budding relationships with gynecological cancers and tried to figure out its role in patient survival outcomes. Total eleven cohort studies (seven cervical and four endometrial cancers) were enrolled. TB showed a poor prognosis in terms of survival and clinicopathological parameters outcome. TB was related to epithelial–mesenchymal transition, microvessel density, and decreased hormone receptor expression. TB can be used as future prognostic marker in gynecologic cancers. ABSTRACT: This study aimed to assess the prognostic significance, assessment methods, and molecular features of tumor budding (TB). A literature search of Medline, EMBASE, Cochrane Library, and eleven cohort studies (seven cervical and four endometrial cancers) was conducted. Three assessment methods for TB involving 2009 patients were collected and constituted in the analysis. Our meta-analysis showed that TB was a marker of poor survival, regardless of the cancer origin site or assessment method (overall survival: hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.82–3.17; disease-free survival: HR, 3.32; 95% CI, 2.46–4.48). In endometrial cancers, TB is associated with the epithelial–mesenchymal transition, microvessel density, and decreased hormone receptor expression. Thus, we suggest TB as a poor prognostic marker for all gynecologic cancers.