Data from Lymphocyte Invasion in IC10/Basal-Like Breast Tumors Is Associated with Wild-Type <i>TP53</i>

Abstract

<div>Abstract<p>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 <i>TP53</i> 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 <i>TP53</i>. 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.</p><p><b>Implications:</b> The association of lymphocytic invasion of ER-negative breast tumors with the retention of wild-type <i>TP53</i> implies a novel protective connection between TP53 function and tumor immunosurveillance. <i>Mol Cancer Res; 13(3); 493–501. ©2014 AACR</i>.</p></div>