The expression of Bcl‐2 family proteins differs between nonsmall cell lung carcinoma subtypes

Abstract

BACKGROUND Proteins of the Bcl‐2 family play a key role in the control of apoptosis and carry out both proapoptotic and antiapoptotic functions. However, with the exception of Bcl‐2 itself, little is known about the expression of these potentially critical proteins in nonsmall cell lung carcinoma. METHODS Immunohistochemistry was used to study the expression of Bcl‐2 and 6 other Bcl‐2 family proteins in a pilot series of 41 archival nonsmall cell lung carcinoma specimens (19 adenocarcinomas and 22 squamous cell carcinomas). RESULTS Overexpression of the apoptosis inhibitors Bcl‐2 and Bcl‐X_L was observed in 10 of 41 samples (24%) and in 11 of 41 samples (27%), respectively. Loss of expression of proapoptotic proteins was observed as follows: Bak, 24 of 41 samples (59%); Bad, 21 of 41 samples (51%); Bid, 20 of 41 samples (49%); Bax, 14 of 41 samples (34%); and Bim/Bod, 2 of 41 samples (5%). Statistically significant differences in expression between adenocarcinoma samples and squamous cell carcinoma samples were observed for Bcl‐X_L (overexpression in 11 of 19 adenocarcinomas [58%] vs. 0 of 22 squamous cell carcinomas [0%]; P < 0.001) and for Bad (loss of expression in 5 of 19 adenocarcinomas [26%] vs. 16 of 22 squamous cell carcinomas [73%]; P = 0.004). CONCLUSIONS Although this was only a pilot study, the results revealed significant differences in the expression of apoptosis‐related proteins both between individual samples of nonsmall cell lung carcinoma and between the two main histologic subtypes. Such differences may play a role in the development of lung tumors; and, if it is found that these differences are of clinical importance, then it may be required to regard nonsmall cell lung carcinoma subtypes as separate entities rather than as one disease. Cancer 2005. © 2005 American Cancer Society.