Szych C, Staebler A, Connolly D C, Wu R, Cho K R, Ronnett B M
Departments of Pathology* and Gynecology and Obstetrics,dagger The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Pathol. 1999 Jun;154(6):1849-55. doi: 10.1016/S0002-9440(10)65442-9.
Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by mucinous ascites and multifocal peritoneal mucinous tumors. Women with PMP often have mucinous tumors involving both the appendix and the ovaries. Several previous histopathological and immunohistochemical studies of PMP have suggested that most, if not all, cases of PMP in women are derived from mucinous adenomas of the appendix rather than from primary ovarian tumors. A few studies of the molecular genetics of PMP have been recently reported. However, these studies analyzed only a small number of cases and some included a heterogeneous group of mucinous tumors, including both benign and malignant appendiceal and ovarian tumors. We analyzed K-ras mutations and allelic losses of chromosomes 18q, 17p, 5q, and 6q in a substantial number of morphologically uniform cases of PMP with synchronous ovarian and appendiceal tumors as well as in appendiceal mucinous adenomas (MAs) and ovarian mucinous tumors of low malignant potential (MLMPs) unassociated with PMP. Each of the 16 PMP cases (100%) analyzed demonstrated identical K-ras mutations in the appendiceal adenoma and corresponding synchronous ovarian tumor. K-ras mutations were identified in 11 of 16 (69%) appendiceal MAs unassociated with PMP and in 12 of 16 (75%) ovarian MLMPs unassociated with PMP. Two PMP cases showed identical allelic losses in the matched ovarian and appendiceal tumors. A discordant pattern of allelic loss between the ovarian and appendiceal tumors at one or two of the loci tested was observed in six PMP cases. In all but one instance, LOH was observed in the ovarian tumor, whereas both alleles were retained in the matched appendiceal lesion, suggesting tumor progression in a secondary (metastatic) site. Our findings strongly support the conclusion that mucinous tumors involving the appendix and ovaries in women with PMP are clonal and derived from a single site, most likely the appendix.
腹膜假黏液瘤（PMP）是一种了解较少的疾病，其特征为黏液性腹水和多灶性腹膜黏液性肿瘤。患有PMP的女性通常有累及阑尾和卵巢的黏液性肿瘤。先前几项关于PMP的组织病理学和免疫组化研究表明，女性中大多数（如果不是全部）PMP病例源自阑尾黏液腺瘤，而非原发性卵巢肿瘤。最近有一些关于PMP分子遗传学的研究报道。然而，这些研究仅分析了少数病例，且有些研究纳入了一组异质性的黏液性肿瘤，包括良性和恶性的阑尾及卵巢肿瘤。我们分析了大量形态学上一致的PMP病例（伴有同步性卵巢和阑尾肿瘤）、阑尾黏液腺瘤（MA）以及与PMP无关的低恶性潜能卵巢黏液性肿瘤（MLMP）中K-ras突变以及18q、17p、5q和6q染色体的等位基因缺失情况。分析的16例PMP病例（100%）中，每例在阑尾腺瘤和相应的同步性卵巢肿瘤中均显示相同的K-ras突变。在16例与PMP无关的阑尾MA中有11例（69%）检测到K-ras突变，在16例与PMP无关的卵巢MLMP中有12例（75%）检测到K-ras突变。2例PMP病例在匹配的卵巢和阑尾肿瘤中显示相同的等位基因缺失。在6例PMP病例中，观察到在一个或两个检测位点上卵巢和阑尾肿瘤之间等位基因缺失的不一致模式。除1例例外，在所有病例中，卵巢肿瘤中观察到杂合性缺失（LOH），而匹配的阑尾病变中两个等位基因均保留，提示肿瘤在继发（转移）部位进展。我们的研究结果有力地支持了这样的结论，即患有PMP的女性中累及阑尾和卵巢的黏液性肿瘤是克隆性的，且源自单一部位，很可能是阑尾。
