Detection of Apoptosis by M30 Monoclonal Antibody in Non-small Cell Lung Carcinomas

Kim, Gwang Il; Lee, Hyeon Jae; Lee, Gun; Lim, Chang Young

Abstract

BACKGROUND: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. MATERIAL AND METHOD: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were performed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. RESULT: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; 61.7+/-26.8 cells vs. p53 negative group; 45.6+/-29.6 cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, AI > or =1) on M30 staining (p53 positive group; 52.4% [11/21] vs. p53 negative group 16.7% [4/24], p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and AI showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% CI 1.886~29.678; p=0.004) and the risk of recurrence almost 3.8-fold (R.R 3.795; 95% CI; 1.184~12.158; p=0.025) in the high AI (> or =1) compared to the low AI (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence.
CONCLUSION
In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.