p53 mutation is infrequent in clear cell carcinoma of the ovary
p53 mutation is infrequent in clear cell carcinoma of the ovary
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DOI：
10.1006/gyno.2000.6025
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发表时间：
2001-02-01
影响因子：
4.7
通讯作者：
Liu, FS
中科院分区：
文献类型：
--
作者：
Ho, ESC;Lai, CR;Liu, FS
Objective. p53基因改变在上皮性卵巢癌中已被广泛研究。然而，它发生在透明细胞癌，一种罕见的组织学亚型上皮性卵巢癌，很少报道。本研究的目的是确定p53基因在这种独特类型的卵巢癌中的改变状态。对38例原发性或复发性卵巢透明细胞癌石蜡切片进行了p53蛋白的研究。所有这些肿瘤进行免疫组化和分子分析。采用单克隆抗体DO-7和PAb 1801进行免疫组化染色，并对38例肿瘤石蜡块提取基因组DNA进行巢式聚合酶链反应/单链构象多态性（PCR/SSCP）分析。SSCP显示条带移位的肿瘤进一步制备用于DNA测序以确定突变位点。p53过表达，观察到只有一个III期透明细胞癌。在免疫组化染色阳性的6例肿瘤中，有4例p53表达改变。三个肿瘤显示错义点突变：两个在外显子7（TCT 227-->TTT和GGC（245）--> AGC），一个在外显子5（CGC（156）--> CAC）。另一个肿瘤显示了两种可能的12-bp缺失：它可能涉及外显子4 3'端的最后四个密码子（核苷酸12，288 - 12，299），或者它可能跨越外显子4和内含子4之间的剪接点（核苷酸12，290 - 12，301）。前者将导致预测的389个氨基酸的蛋白质产物，而后者将导致基因序列的移码，并将导致截短的蛋白质。p53突变在透明细胞癌中的发生率似乎比其他组织学类型的上皮性卵巢癌低得多。我们认为，p53的改变可能不会发挥重要作用，在透明细胞癌的发展。
Objective. p53 gene alteration has been extensively studied in epithelial ovarian cancer. However, its occurrence in clear cell carcinoma, an infrequent histologic subtype of epithelial ovarian cancer, is rarely reported. The aim of this study is to determine the status of p53 gene alteration in this distinct type of ovarian carcinoma.Methods. Paraffin blocks of tumors from 38 patients with primary or recurrent ovarian clear cell carcinoma were studied for p53 alteration. All these tumors were subjected to immunohistochemical and molecular analysis. Two monoclonal antibodies (DO-7 and PAb 1801) were used for immunohistochemical staining, Genomic DNAs extracted from paraffin blocks of the 38 tumors were subscribed for a nested polymerase chain reaction/ single-strand conformation polymorphism (PCR/SSCP) analysis. Tumors showing band shift on SSCP were further prepared for DNA sequencing to determine the site of mutation.Results. Overexpression of p53 was observed in only one stage III clear cell carcinoma. However, focal positive p53 staining was noted in another five tumors, Of the six tumors showing positive immunohistochemistry, p53 alterations were noted in four tumors. Three tumors revealed a missense point mutation: two were in exon 7 (TCT227 -->TTT and GGC(245) --> AGC) and one was in exon 5 (CGC(156) --> CAC). Another tumor revealed a 12-bp deletion in two possible ways: it might involve the last four codons at the 3' end of exon 4 (nucleotides 12,288-12,299) or it might cross over the splice junction between exon 4 and intron 4 (nucleotides 12,290-12,301). The former would result in a predicted protein product of 389 amino acids whereas the latter would cause a frameshift in the gene sequence and would result in a truncated protein.Conclusion. Mutations in p53 appear to be much less frequent in clear cell carcinoma than in other histologic types of epithelial ovarian cancer. We suggest that p53 alterations may not play an important role in the development of clear cell carcinoma.