Influence of Apoptosis and Cell Cycle Regulator Proteins on Chemotherapy Response and Survival in Stage IIIA/IIIB NSCLC Patients

Abstract

Prognosis for non-small cell lung cancer (NSCLC) patients is very poor. Prediction of the response to treatment in individual patients may be possible using molecular biological alterations such as clinical biomarkers. We investigated the predictive value of apoptosis and cell cycle regulator proteins for neoadjuvant chemotherapy response in stage IIIA/IIIB NSCLC patients. We evaluated p53, bcl-2, p21WAF1/CIP1, p27Kip1, and Ki67 immunohistochemical expression and apoptotic index in mediastinal lymph node metastases from 23 IIIA and 10 IIIB NSCLC patients before treatment with neoadjuvant platinum-based chemotherapy. Univariate analysis was performed to evaluate the relationship between protein expression and survival or time to progression (TTP). Median follow-up was 25 months (range, 4-112), median TTP was 11 months (range, 0-112), and median overall survival was 22 months (range, 4-112). Of 32 assessable patients, 18 (56%) had stable disease, 12 (38%) had a PR, and two (6%) had progressive disease. Of the 22 patients assessable for pN2 following chemotherapy, 16 (77%) were positive. Univariate analysis showed that shorter TTP correlated with progressive disease (p = 0.000), positive pN2 after chemotherapy (p = 0.026), high Ki67 (p = 0.022), and high p21WAF1/CIP1 (p = 0.038). Our results suggest that in IIIA/IIIB NSCLC patients, a high level of p21WAF1 expression in mediastinal lymph node metastases before neoadjuvant platinum-based chemotherapy is associated with a poor outcome. Our results suggest that expression of p21WAF1, which plays a role in preventing apoptosis, may be significant when selecting chemotherapy for NSCLC patients.