Transglutaminase II expression in invasive ductal carcinomas.

Abstract

34 Background: Molecular markers for predicting breast cancer patients at high risk of recurrence are urgently needed for more effective disease management. The impact of alterations in extracellular matrix components on tumor aggressiveness is under intense investigation. Overexpression of Transglutaminase 2 (TG2), a multifunctional enzyme, in cancer cells impacts epithelial mesenchymal transition and cancer stem cell phenotype, growth, invasion and interactions with tumor microenvironment. The objective of our study is to determine the clinical relevance of stromal TG2 overexpression and explore its potential to identify which IDCs are at high risk of recurrence. Methods: This retrospective study is based on immunohistochemical analysis of TG2 expression in 168 invasive ductal carcinomas with clinical, pathological and follow-up data available for up to 12 years. TG2 expression was correlated with clinical and pathological parameters as well as disease free survival (DFS) of breast cancer patients. Results: Stromal TG2 overexpression was observed in 97/168 (57.7%) invasive ductal carcinomas (IDC). Notably, IDC patients showing stromal TG2 accumulation had significantly reduced disease free survival (mean DFS = 110 months) in comparison with patients showing low expression (mean DFS = 130 months), as revealed by Kaplan-Meier survival analysis (p <0.001). In Cox multivariate regression analysis, TG2 accumulation in tumor stroma emerged as an independent risk factor for recurrence in IDC (p = 0.006, Hazard’s ratio, H.R. = 3.79). Conclusions: Accumulation of TG2 in tumor stroma is an independent risk factor for identifying breast cancer patients at high risk of recurrence. TG2 overexpression in tumor stroma may serve as a predictor of poor prognosis for IDC of the breast.