PCNA and anti-apoptotic Mcl-1 proteins predict disease-free survival in oral cancer patients treated with definitive radiotherapy

Abstract

At our laboratory, we recently observed cell cycle and apoptosis-related proteins Myeloid Cell Leukemia-1 (Mcl-1) and Proliferating Cell Nuclear Antigen (PCNA) to be altered in oral tumours/cell lines. The present study aimed to evaluate the above proteins for predicting response and outcome in oral cancer patients treated with definitive radiotherapy. Pre-treatment oral cancer biopsy samples from 39 patients were examined for Mcl-1 and PCNA proteins using immunohistochemistry and correlated with clinico-pathological variables using disease-free survival (DFS) as the primary endpoint. We observed high expression of Mcl-1 in older versus younger patients (p=0.013) and in tobacco chewers+/-alcohol versus smokers+/-alcohol (p=0.037); and PCNA in node-positive versus node-negative tumours (p=0.037). On univariate analysis, high PCNA (p=0.007), Mcl-1 (p=0.050), node positivity (p=0.040) and co-expression of PCNA and Mcl-1 (p=0.008), had a significant impact on DFS. On multivariate analysis, low PCNA/Mcl-1 (p=0.006) co-expressing tumours were associated with improved DFS. Thus our study suggests that in patients undergoing primary radiotherapy, PCNA could be of potential predictive value to identify patients with risk of nodal metastases and in combination with Mcl-1 may have potential prognostic value to differentiate patients with poor DFS. These markers may be used for future trial patients requiring radiotherapy for their treatment.