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From the Departments of Pathology*
and Gynecology
and Obstetrics,
The Johns Hopkins University
School of Medicine, Baltimore, Maryland
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.
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