ABSTRACT
Survivin is an inhibitor of apoptosis that plays a significant role in cell cycle regulation and is important for survival prognosis in many neoplasms. Survivin expression was assessed by in situ hybridization (ISH) in 60 consecutive patients (54 males and 4 females) with NSCLC treated between 1993 and 1997. The examined patients had IIB and IIIA stage according to TNM system. In all cases the chemotherapy with cisplatin and etoposide (2 cycles) was administered prior the surgery; in patients responding to the therapy one more cycle was applied. Survivin gene overexpression was observed in 35 patients (58.3%). There was no correlation between survivin mRNA level and histological type of tumor, stage of cell differentiation, stage of disease according to TNM classification, performance status according to WHO and number of chemotherapy regimens administered (p > 0.05). However, the correlation between survivin gene expression and response to the chemotherapy was statistically significant (p = 0.04). Statistical analysis showed that median survival in patients with survivin gene overexpression was shorter (14.0 months) as compared to patients with no expression (60.0 months; p = 0.00002). In survival assessment by means of Kaplan-Meier test, 14.3% of five-year survival was achieved in the former group versus 60% in the latter (p = 0.00003). Univariate analysis (log-rank test) showed that significant independent prognostic factors in NSCLC included: stage of the disease according to TNM classification (p = 0.006), response to chemotherapy (p = 0.005) and pattern of survivin gene expression (p = 0.00003). Multivariate analysis utilizing Cox's model showed that for survival assessment the stage according to TNM, response to the chemotherapy and survivin expression estimated by means of ISH are of statistical significance (p=0.00001). The calculated predictive values showed that ISH technique was quite accurate in assessment of five-year survival. Our data show that survivin expression may be used as a prognostic factor and a target for therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gene Expression Regulation, Neoplastic/genetics , In Situ Hybridization, Fluorescence/methods , Lung Neoplasms/genetics , Microtubule-Associated Proteins/genetics , Neoplasm Proteins/genetics , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Apoptosis/physiology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , Female , Humans , Inhibitor of Apoptosis Proteins , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Microtubule-Associated Proteins/biosynthesis , Microtubule-Associated Proteins/metabolism , Middle Aged , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/metabolism , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , Retrospective Studies , Sensitivity and Specificity , Survival Analysis , Survivin , Treatment OutcomeABSTRACT
The results of lung cancer treatment have not significantly improved for many years. About 35% of patients with non-small cell lung cancer (NSCLC) are in clinical stage IIIA. Clinically asymptomatic distant metastases occur in the majority of these patients. In such cases only combined treatment offers a chance of cure. In the Chest Surgery Center in Lublin a clinical trial was carried out aimed to assess late results of combined treatment in patients with IIIA NSCLC. Over 700 patients were enrolled in the study. The results of the trial disclosed, that neoadjuvant chemotherapy prolonged life of the operated patients and improved their life quality. However, a question of qualification for this complex treatment and complexity of assessment criteria, still remain to be answered.