Tumor Budding, Cell Nest Size, and HER2 Expression as Prognostic Determinants in Gastric-Type Endocervical Adenocarcinoma

The prognostic determinants of gastric-type adenocarcinoma (GAC) remain poorly defined. In this study, we evaluated the prognostic significance of the tumor budding and cell nest size-based (TBNS) grading scheme, HER2 and p53 expression in a single-institution cohort of 146 consecutive GAC patients. Perineural invasion (PNI), lymph node metastasis, FIGO stage III/IV disease, high tumor budding activity, single-cell invasion, TBNS grade 3, and HER2 positivity were all significantly associated with worse overall survival (OS) and progression-free survival (PFS) (all P<0.05). In multivariable Cox regression analysis, FIGO stage III/IV and HER2 positivity emerged as independent predictors of worse PFS and OS (both P<0.05). Among patients with FIGO stage I/II disease, PNI, mutant-type p53 expression, and HER2 positivity were identified as significant determinants of adverse outcomes. Mutant-type p53 expression was associated with significantly worse 2- and 5-year PFS and OS (all P<0.05). In conclusion, our study confirms the prognostic value of FIGO stage, the TBNS grading scheme, and HER2 expression in GAC. In patients with FIGO stage I/II disease, PNI, HER2 positivity, and mutant-type p53 expression represent key determinants of poor prognosis. These findings may inform clinical decision-making and risk-adapted treatment strategies, pending prospective multi-institutional validation.