Triple-negative breast carcinomas represent a tumor group of pivotal clinical importance given the lack of target therapies. The prognostic significance of triple-negative breast carcinomas remains unclear because of their histological and molecular heterogeneity. Currently, neither prognostic nor predictive factors are available for these tumors. Retinoblastoma (Rb) pathway loss has been linked to clinical outcome in various cancer types, including breast cancer. We investigated the association between Rb and p16 protein expression and clinical outcome in no-special-type triple-negative breast carcinomas. Immunohistochemical staining for Rb, p16, p53 and CK5 was carried out on a section from archival specimens of 117 no-special-type triple-negative breast carcinomas. Immunopositive p16 (p16þ) and immunonegative Rb (Rb) staining were seen in 49.5% and in 24.8% of tumors, respectively. There was an inverse correlation between p16þ and Rb (Po0.001). P16þ was correlated with G3 grade (Po0.001), high Ki-67 (P¼0.03), p53 overexpression (Po0.001) and CK5 immunopositivity (P¼0.01). Rb was not associated with any clinicopathologic variable. Follow-up and therapy data were available in 95 patients. In 20 patients treated with surgery only, neither p16þ nor Rb immunostaining were associated with disease-free survival and overall survival. In 75 patients treated with adjuvant chemotherapy, p16þ was associated with good response to therapy with significant increased disease-free survival (P¼0.001) and showed a trend towards a statistical significance for increased overall survival (P¼0.056); Rb were not associated with disease-free survival and overall survival. In multivariate analysis, p16þ was independently associated with disease-free and overall survival, with a hazard ratio of 0.18 (95% CI: 0.06–0.51; P¼0.001) and 0.21 (95% CI: 0.06–0.74; P¼0.015), respectively. In patients with no-specialtype triple-negative breast carcinomas, p16þ is related to good response to adjuvant chemotherapy and can be considered the best surrogate marker for Rb pathway loss. Modern Pathology advance online publication, 26 July 2013; doi:10.1038/modpathol.2013.137
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