Subtype-dependent prognostic significance of Ki-67, histological grade, and vascular invasion in breast and colorectal cancer

Abstract

Traditional pathological markers remain relevant in prognostic assessment for solid tumors, but their clinical value may differ according to tumor biological context. This study evaluated the prognostic significance of Ki-67, histological grade, and vascular invasion (VI) in breast and colorectal cancer, with emphasis on subtype-specific differences. This single-center retrospective cohort included 846 patients with breast cancer or colorectal cancer who underwent curative-intent surgery between 2015 and 2022. Ki-67 expression, histological grade, and VI were extracted from pathological records. The pooled analysis was designed as an exploratory cross-cancer comparison of shared pathological features rather than as an assumption of biological equivalence between the 2 malignancies; cancer-specific and molecular-context analyses were therefore emphasized. Overall survival was assessed using Cox proportional hazards regression, with subgroup analyses according to breast cancer surrogate molecular subtype and colorectal cancer mismatch repair status. A simple Ki-67/VI score was explored for risk stratification. In multivariable analysis, increased age, stage III disease, high Ki-67 expression, and VI were independently associated with worse overall survival, whereas histological grade was not retained as an independent predictor. In breast cancer, the prognostic effect of Ki-67 was evident in luminal B and triple-negative subtypes but not in luminal A disease. In colorectal cancer, VI showed stronger prognostic value in proficient mismatch repair tumors than in deficient mismatch repair tumors. The combined Ki-67/VI score provided incremental prognostic stratification and showed better discriminatory performance than any single marker alone. Ki-67 and VI were associated with prognosis in this retrospective cohort, and the magnitude of these associations varied according to tumor biological context. The Ki-67/VI score should be regarded as exploratory and hypothesis-generating pending internal optimism correction and external validation. Interpretation of conventional pathological indicators should therefore remain cancer- and subtype-specific.