Survivin Expression in Non–small-cell Lung Carcinomas: Correlation With Apoptosis and Other Apoptosis-related Proteins, Clinicopathologic Prognostic Factors and Prognosis

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Abstract

The role of survivin that regulates the biological behavior of non–small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P=0.04, r=−0.367), and tumor stage (P=0.03, r=−0.273), and positively correlated with tumor cell proliferation (P=0.009, r=0.329). Cytoplasmic survivin expression positively correlated with smoking history (P=0.02, r=0.282). Survivin/bax ratio was inversely correlated with AI (r:−0.004). By Kaplan-Meier analysis, TNM stage (P≤0.001), lymph node metastasis (P=0.04), and Ki-67 index (P≤0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.

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