Marchenko N D, Moll U M
Department of Pathology, University Hospital, State University of New York at Stony Brook, 11794-8691, USA.
Hum Pathol. 1997 Sep;28(9):1002-6. doi: 10.1016/s0046-8177(97)90051-4.
Primary peritoneal carcinoma (PPC) is an aggressive malignancy of the female coelomic epithelium. Previously we had analyzed 29 cases of PPC for p53 protein accumulation by immunocytochemistry. P53 was overexpressed in 83% (24 of 29) of PPCs, including 21 tumors with diffuse intense staining of 100% of tumor nuclei and three additional tumors with significant focal staining. Here we report results of a mutational analysis on the entire p53 coding sequence of 22 of these cases (comprising 18 p53-positive and four negative tumors), using single-strand conformation polymorphism (SSCP) and direct sequence analysis. Only 2 of 22 (9%) patients harbored a p53 mutation (which, interestingly, were identical and consisted of a codon 259 Asp --> His exchange), despite diffuse overexpression of high levels of nuclear p53 protein in most cases. This result indicates that (1) the abnormal p53 expression is usually not caused by mutations of the p53 gene in PPC and (2) PPC is part of a growing number of tumors that share evidence of p53 dysfunction in the absence of mutation.
原发性腹膜癌（PPC）是女性体腔上皮的侵袭性恶性肿瘤。此前我们通过免疫细胞化学分析了29例PPC中p53蛋白的积聚情况。83%（29例中的24例）的PPC中p53过表达，其中21个肿瘤100%的肿瘤细胞核呈弥漫性强染色，另外3个肿瘤有明显的局灶性染色。在此我们报告对其中22例病例（包括18例p53阳性和4例阴性肿瘤）的整个p53编码序列进行突变分析的结果，采用单链构象多态性（SSCP）和直接测序分析。尽管大多数病例中核p53蛋白弥漫性高表达，但22例患者中只有2例（9%）存在p53突变（有趣的是，这两个突变相同，均为密码子259天冬氨酸→组氨酸交换）。这一结果表明：（1）PPC中p53表达异常通常不是由p53基因突变引起的；（2）PPC是越来越多在无突变情况下存在p53功能障碍证据的肿瘤之一。
