Molecular genetic evidence supporting the clonality and appendiceal originof pseudomyxoma peritonei in women

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 fro m mucinous adenomas of the appendix rather than from primary ovarian tumors . A few studies of the molecular genetics of PMP have been recently reporte d. However, these studies analyzed only a small number of cases and some in cluded a heterogeneous group of mucinous tumors, including both benign and malignant appendiceal and ovarian tumors. We analyzed K-ras mutations and a llelic losses of chromosomes 18q, 17p, 5q, and 6q in a substantial number o f morphologically uniform cases of PMP with synchronous ovarian and appendi ceal tumors as well as in appendiceal mucinous adenomas (MAs) and ovarian m ucinous tumors of low malignant potential (MLMPs) unassociated with PIMP. E ach of the 16 PMP cases (100%) analyzed demonstrated identical K-ras mutati ons in the appendiceal adenoma and corresponding synchronous ovarian tumor. K-ras mutations were identified in 11 of 16 (69%) appendiceal MAs unassoci ated with PMP and in 12 of 16 (75%) ovarian MLMPs unassociated with PMP. Tw o PMP cases showed identical allelic losses in the matched ovarian and appe ndiceal tumors. A discordant pattern of allelic loss between the ovarian an d appendiceal tumors at one or two of the loci tested was observed in six P MP cases. In all but one instance, LOH was observed in the ovarian tumor, w hereas both alleles were retained in the matched appendiceal lesion, sugges ting tumor progression in a secondary (metastatic) site. Our findings stron gly support the conclusion that mucinous tumors involving the appendix acid ovaries in women with PMP are clonal and derived from a single site, most Likely the appendix.