D Quigley, L Silwal-Pandit, R Dannenfelser, A Langerød, HKM Vollan, C Vaske, JU Siegel, O Troyanskaya, S-F Chin, C Caldas, A Balmain, A-L Børresen-Dale, V Kristensen
Mol Cancer Res
UNLABELLED: Lymphocytic infiltration is associated with better prognosis in several epithelial malignancies including breast cancer. The tumor suppressor TP53 is mutated in approximately 30% of breast adenocarcinomas, with varying frequency across molecular subtypes. In this study of 1,420 breast tumors, we tested for interaction between TP53 mutation status and tumor subtype determined by PAM50 and integrative cluster analysis. In integrative cluster 10 (IC10)/basal-like breast cancer, we identify an association between lymphocytic infiltration, determined by an expression score, and retention of wild-type TP53. The expression-derived score agreed with the degree of lymphocytic infiltration assessed by pathologic review, and application of the Nanodissect algorithm was suggestive of this infiltration being primarily of cytotoxic T lymphocytes (CTL). Elevated expression of this CTL signature was associated with longer survival in IC10/Basal-like tumors. These findings identify a new link between the TP53 pathway and the adaptive immune response in estrogen receptor (ER)-negative breast tumors, suggesting a connection between TP53 inactivation and failure of tumor immunosurveillance. IMPLICATIONS: The association of lymphocytic invasion of ER-negative breast tumors with the retention of wild-type TP53 implies a novel protective connection between TP53 function and tumor immunosurveillance.