DNA Damage Repair Proteins, HSP27, and Phosphorylated-HSP90α as Predictive/Prognostic Biomarkers of Platinum-based Cancer Chemotherapy: An Exploratory Study

Platinum analogs are commonly used for cancer treatment. There is increasing interest in finding biomarkers which could predict and overcome resistance, because to date there is no reliable predictive/prognostic marker for these compounds. Here we studied the immunohistochemical expression of proteins involved in DNA damage response and repair (gamma H2AX, 53BP1, ERCC1, MLH1, and MSH2) in primary tumor tissues from patients treated with platinum-based chemotherapy. Levels and localization of Heat Shock Protein (HSP)27 and phospho-(Thr5/7)-HSP90 alpha (p-HSP90 alpha) were also determined. The implications in clinical response, disease-free survival and overall survival were analyzed. High gamma H2AX and 53BP1 expressions were associated with poor clinical response. Nuclear p-HSP90 alpha, as well as nuclear absence and low cytoplasmic expression of HSP27 correlated with good response. Patients with high gamma H2AX and high cytoplasmic HSP27 expressions had shorter overall survival and disease-free survival. MLH1, MSH2, or ERCC1 were not associated with clinical response or survival. We report the potential utility of p-HSP90 alpha, HSP27, gamma H2AX, and 53BP1 as predictive/prognostic markers for platinum-based chemotherapy. We present the first study that evaluates the predictive and prognostic value of p-HSP90 alpha in primary tumors. Our research opens new possibilities for clinical oncology and shows the usefulness of immunohistochemistry for predicting chemotherapy response and prognosis in cancer.