Watson A J, Merritt A J, Jones L S, Askew J N, Anderson E, Becciolini A, Balzi M, Potten C S, Hickman J A
Department of Medicine, University of Manchester, Hope Hospital, Salford, UK.
Br J Cancer. 1996 Apr;73(8):889-95. doi: 10.1038/bjc.1996.178.
Evidence of accumulating for the failure of apoptosis as an important factor in the evolution of colorectal cancer and its poor response to adjuvant therapy. The proto-oncogene bcl-2 suppresses apoptosis. Its expression could provide an important survival advantage permitting the development of colorectal cancer. The expression of bcl-2 and p53 was determined by immunohistochemistry in 47 samples of histologically normal colonic mucosa, 19 adenomas and 53 adenocarcinomas. Expression of bcl-2 in colonic crypts > 5 cm from the tumours was confined to crypt bases but was more extensive and intense in normal crypts < 5 mm from cancers. A higher proportion of adenomas (63.2%) than carcinomas (36.5%) expressed bcl-2 (P < 0.05). A lower proportion of adenomas (31.6%) than carcinomas (62.3%) expressed p53 (P < 0.02). A total of 26.3% of adenomas and 22% of carcinomas expressed both bcl-2 and p53. To determine whether these samples contained cells which expressed both proteins, a dual staining technique for bcl-2 and p53 was used. Only 1/19 adenomas and 2/53 carcinomas contained cells immunopositive for both bcl-2 and p53. Moreover there was evidence of reciprocity of expression of bcl-2 and p53 in these three double staining neoplasms. We suggest that bcl-2 provides a survival advantage in the proliferative compartment of normal crypts and colorectal neoplasms. However, its expression is lost during the evolution from adenoma to carcinoma, whereas p53 expression is increased, an event generally coincident with the expression of stabilised p53, which we presume to represent the mutant form.
越来越多的证据表明，细胞凋亡失败是结直肠癌发生发展及其对辅助治疗反应不佳的重要因素。原癌基因bcl-2可抑制细胞凋亡。其表达可能提供重要的生存优势，从而促使结直肠癌的发生。采用免疫组织化学方法检测了47例组织学正常的结肠黏膜、19例腺瘤和53例腺癌组织中bcl-2和p53的表达。距肿瘤>5 cm的结肠隐窝中bcl-2的表达仅限于隐窝底部，但在距癌<5 mm的正常隐窝中更为广泛和强烈。表达bcl-2的腺瘤比例（63.2%）高于癌（36.5%）（P<0.05）。表达p53的腺瘤比例（31.6%）低于癌（62.3%）（P<0.02）。共有26.3%的腺瘤和22%的癌同时表达bcl-2和p53。为确定这些样本中是否含有同时表达这两种蛋白的细胞，采用了bcl-2和p53双重染色技术。仅1/19例腺瘤和2/53例癌含有bcl-2和p53免疫阳性细胞。此外，在这3例双重染色的肿瘤中存在bcl-2和p53表达的相互关系。我们认为，bcl-2在正常隐窝和结直肠肿瘤的增殖区提供生存优势。然而，在从腺瘤向癌的演变过程中其表达丧失，而p53表达增加，这一事件通常与稳定型p53的表达一致，我们推测其代表突变形式。
