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

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 < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 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.

Expression of HuR, COX-2, and survivin in lung cancers; cytoplasmic HuR stabilizes cyclooxygenase-2 in squamous cell carcinomas

“…Third, it may be due to the variable criteria used to classify a tumor as having more nuclear survivin or cytoplasmic survivin. 24,29,46 As the balance between cytoplasmic and nuclear survivin in tumor cells may be considered as an indicator for 'active survivin,' it is advisable to quantify not only absolute expression levels, but also the relative intracellular localization of survivin, cytoplasmic, nuclear, total (cytoplasmic þ nuclear), and the difference in survivin expression (cytoplasmic -nuclear). 45 Our results showed that cytoplasmic survivin (log rank test, adenocarcinoma, Po0.001; squamous cell carcinoma, P ¼ 0.005) and the difference in survivin (log rank test, adenocarcinoma, Po0.001; squamous cell carcinoma, P ¼ 0.014) was associated with a poorer survival rate, whereas nuclear survivin expression (log rank test, adenocarcinoma, P ¼ 0.006; squamous cell carcinoma, P ¼ 0.050) was associated with a favorable survival rate.…”

“…The relationship of nuclear versus cytoplasmic expression of survivin with apoptosis and the expression of HuR-related COX-2 expression is not well characterized in primary human lung cancers. [23][24][25][26][27][28][29][30][31] In this study, we evaluated the expression of survivin, COX-2, and HuR, and subcellular localization of survivin and HuR in sets of pulmonary adenocarcinomas and squamous cell carcinomas patients, in relation to clinicopathologic parameters and survival. In addition, we investigated the relation of survivin, COX-2, and HuR expression.…”

Induction of apoptosis of non-small cell lung cancer by a methylated oligonucleotide targeting survivin gene

“…[4][5][6][7][8][9] Recent studies have also shown that survivin expression levels correlate with oncogenesis, aggressiveness of tumors and poor clinical outcome in NSCLC. [10][11][12][13][14][15] To target survivin overexpression as a cause of lung cancer, strategies have been designed to inhibit survivin synthesis with the hope of preventing or mitigating NSCLC. [16][17] DNA methylation is a critical epigenetic modification that silences gene transcription.…”

&lt;i&gt;Survivin&lt;/i&gt; promoter rs9904341 polymorphism is associated with tumor stage and grade in patients with bladder cancer

“…Previous studies have reported that increased survivin expression was associated with various cancers including bladder, colorectal, lung and oral [6][7][8][9][10]. A previous study reported that survivin was detected in urine samples from patients with new or recurrent bladder cancer but not found from healthy volunteers [11].…”