Moskaluk C A, Heitmiller R, Zahurak M, Schwab D, Sidransky D, Hamilton S R
Department of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD, USA.
Hum Pathol. 1996 Nov;27(11):1211-20. doi: 10.1016/s0046-8177(96)90317-2.
The WAF1 (CIP1/SDI1) gene encodes a cyclin-dependent kinase inhibitor which is induced by wild-type, but not mutated, p53 gene product. WAF1 immunohistochemistry has been suggested to clarify the phenotype of overexpressed p53 gene product. We evaluated both p53 and WAF1 gene products by immunohistochemistry in 98 esophagectomy specimens with Barrett esophagus and/or adenocarcinoma of the esophagus and esophagogastric junction. Diffuse positive p53 staining was found in 40 of 88 adenocarcinomas (45%) and in dysplastic Barrett epithelium in 20 of 65 cases (31%), but not in Barrett mucosa without dysplasia (n = 36, P = .0004). Eighty-eight percent of cancers exhibited WAF1 expression, but there was no association with p53 and WAF1 staining. WAF1 protein was also identified in Barrett epithelium and in esophageal squamous and gastric epithelium. In contrast to carcinomas, a unique pattern of mutually exclusive p53 and WAF1 expression was found in five cases of dysplastic Barrett epithelium; a missense mutation at codon 175 of p53 was identified in one. p53 staining of adenocarcinoma was associated with shorter patient survival but was not independent of stage; WAF1 status added no prognostic information. Our findings show that WAF1 immunohistochemistry complements p53 immunohistochemistry in some cases of Barrett dysplasia but not in adenocarcinomas. Positive p53 immunostaining can serve to confirm a neoplastic process in Barrett mucosa. Positive staining of adenocarcinomas may be an indication of advanced stage.
WAF1（CIP1/SDI1）基因编码一种细胞周期蛋白依赖性激酶抑制剂，它由野生型而非突变型p53基因产物诱导产生。有人提出，WAF1免疫组织化学可用于阐明过表达的p53基因产物的表型。我们通过免疫组织化学对98例伴有巴雷特食管和/或食管腺癌及食管胃交界腺癌的食管切除标本中的p53和WAF1基因产物进行了评估。在88例腺癌中有40例（45%）出现弥漫性p53阳性染色，在65例发育异常的巴雷特上皮中有20例（31%）出现阳性染色，但在无发育异常的巴雷特黏膜中未出现（n = 36，P = 0.0004）。88%的癌症表现出WAF1表达，但p53和WAF1染色之间无关联。在巴雷特上皮以及食管鳞状上皮和胃上皮中也鉴定出了WAF1蛋白。与癌不同，在5例发育异常的巴雷特上皮中发现了p53和WAF1表达相互排斥的独特模式；其中1例鉴定出p53第175密码子的错义突变。腺癌的p53染色与患者生存期较短相关，但并非独立于分期；WAF1状态未提供预后信息。我们的研究结果表明，在某些巴雷特发育异常病例中，WAF1免疫组织化学可补充p53免疫组织化学，但在腺癌中并非如此。p53免疫染色阳性可用于确认巴雷特黏膜中的肿瘤形成过程。腺癌的阳性染色可能提示疾病处于晚期。
