Berrieman Helen K, Smith Laura, O'Kane Sara L, Campbell Anne, Lind Michael J, Cawkwell Lynn
Postgraduate Medical Institute of the University of Hull, Hull-York Medical School, University of Hull, Hull, United Kingdom.
Cancer. 2005 Apr 1;103(7):1415-9. doi: 10.1002/cncr.20907.
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.
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).
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).
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.
Bcl-2家族蛋白在细胞凋亡调控中起关键作用，兼具促凋亡和抗凋亡功能。然而，除Bcl-2本身外，对于这些潜在关键蛋白在非小细胞肺癌中的表达情况知之甚少。
采用免疫组织化学方法，对41例存档的非小细胞肺癌标本（19例腺癌和22例鳞状细胞癌）组成的试验系列进行Bcl-2及其他6种Bcl-2家族蛋白表达情况的研究。
凋亡抑制蛋白Bcl-2和Bcl-X(L)的过表达分别在41个样本中的10个（24%）和11个（27%）样本中被观察到。促凋亡蛋白表达缺失情况如下：Bak，41个样本中的24个（59%）；Bad，41个样本中的21个（51%）；Bid，41个样本中的20个（49%）；Bax，41个样本中的14个（34%）；以及Bim/Bod，41个样本中的2个（5%）。在腺癌样本和鳞状细胞癌样本之间，观察到Bcl-X(L)（19例腺癌中有11例[58%]过表达，而22例鳞状细胞癌中无过表达[0%]；P<0.001）和Bad（19例腺癌中有5例[26%]表达缺失，而22例鳞状细胞癌中有16例[73%]表达缺失；P = 0.004）在表达上存在统计学显著差异。
尽管这只是一项初步研究，但结果显示非小细胞肺癌个体样本之间以及两种主要组织学亚型之间在凋亡相关蛋白表达上存在显著差异。这些差异可能在肺肿瘤发生中起作用；并且，如果发现这些差异具有临床重要性，那么可能需要将非小细胞肺癌亚型视为不同实体而非一种疾病。
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