Correlations between Proliferative-apoptotic Activity of Breast Epithelial Tumours and Precancerous Conditions, Tumour “Buds” and Tumour-infiltrating Lymphocytes: a Retrospective Immunohistochemical Study

Breast carcinoma exhibits significant biological heterogeneity, characterised by marked differences in proliferative activity, apoptotic regulation, invasive potential, and immune microenvironment. Growing evidence suggests that the interplay among these factors significantly contributes to tumour progression and heterogeneous clinical behaviour. This study aimed to investigate the relationship between proliferative activity, expression of apoptotic markers, tumour “buds” and tumour-infiltrating lymphocytes (TIL) in epithelial breast tumours and pre-tumour states.

This retrospective study included benign, preinvasive, and invasive breast epithelial lesions diagnosed between 2018 and 2025. Histopathological evaluation was performed using hematoxylin and eosin-stained slides. Immunohistochemical analysis included Ki67 as a proliferative marker and BCL2 as an anti-apoptotic marker. Tumour “grids” were assessed at the invasive front, and stromal TILs were assessed according to established international recommendations. Statistical analysis was performed using nonparametric methods for comparison and correlation. A total of 54 cases were included in the study, including benign/hyperplastic lesions, preinvasive lesions, and invasive breast carcinoma. Ki67 expression showed a progressive increase across the neoplastic spectrum, with the highest proliferative activity observed in invasive carcinomas and especially in triple-negative tumours (p < 0.001). Tumour “seeding” activity showed a strong positive correlation with Ki67 expression (rho = 0.949, p < 0.001), indicating a close relationship between proliferative activation and invasive remodelling. Stromal TIL density showed an inverse correlation with both Ki67 expression and tumour “budding” activity, indicating a relative suppression of the local immune response in highly aggressive tumours. BCL2 expression differed significantly between lesion groups (p < 0.001), although its association with recurrence was not statistically significant.

Breast cancer progression is associated with coordinated changes in proliferative signalling, apoptotic regulation, invasive morphological remodelling, and stromal immune response. High Ki67 expression and tumour growth appear to be interrelated indicators of aggressive tumour behaviour, while decreased stromal TIL density may reflect progressive immune escape during tumour evolution. Integrated assessment of proliferative, apoptotic, and microenvironmental parameters may provide valuable additional information for the biological stratification of breast carcinoma.