Pseudomyxoma Peritonei Is a Disease of MUC2-Expressing Goblet Cells

Abstract

Pseudomyxoma peritonei, a syndrome first described by Karl F. Rokitansky in 1842, is an enigmatic, often fatal intra-abdominal disease characterized by dissecting gelatinous ascites and multifocal peritoneal epithelial implants secreting copious globules of extracellular mucin. Although past interest in the syndrome has focused on the questions of the site of origin (appendix versus ovary), mechanisms of peritoneal spread (multicentricity, redistribution phenomenon, or metastasis), and the degree of malignant transformation present (adenoma, borderline tumor, or carcinoma), another important question is the mechanism behind the accumulation of extracellular mucin, the real cause of the disease's morbidity and mortality irrespective of the site of origin, mechanism of peritoneal spread, or transformed status of its epithelium. Taking advantage of the recently cloned human mucin genes, we decided to investigate this question. Our studies revealed that pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells. These cells also express MUC5AC but the latter mucin is not specific for pseudomyxoma peritonei. MUC2 expression accounts for the voluminous deposits of extracellular mucin (mucin:cell ratios exceeding 10:1) and distinguishes pseudomyxoma peritonei secondarily involving the ovary from primary ovarian mucinous tumors with peritoneal implants. Because mucinous tumors of the appendix similarly express MUC2, the MUC2 expression profile also supports an appendiceal rather than ovarian origin for pseudomyxoma peritonei.

MUC2 Is a Molecular Marker for Pseudomyxoma Peritonei

“…Our recent molecular studies with pseudomyxoma peritonei and derived primary cell cultures have indicated that MUC2 expression is epigenetically regulated and susceptible to pharmacological regulation (42). This suggests that MUC2 may also be the primary molecular target for pseudomyxoma peritonei as well.…”

Leptin, MUC2 and mTOR in Appendiceal Mucinous Neoplasms

“…This result is consistent with the results of previous reports. In 2002, O'Connell et al [8] demonstrated that MUC2 served as a reliable molecular marker of pseudomyxoma peritonei. In 2008, Semino-Mora et al [10] reported that the expression of MUC2 was drastically higher in peritoneal-free mucin and in mucinous neoplastic epithelia of pseudomyxoma peritonei compared with non-neoplastic appendiceal epithelia; additionally, these authors found that multiple enteric bacteria were present in pseudomyxoma peritonei and that bacterial density and MUC2 expression were higher in peritoneal-free mucin of pseudomyxoma peritonei compared with controls.…”

Pseudomyxoma peritonei Manifesting as Umbilical Hernia: Report of a Case and Review of the Literature

“…The rest lie somewhere in between and are classed as hybrids, which means the mucinous adenocarcinoma presents a hybrid pattern of distribution that shows features of the pattern seen with adenocarcinoma combined with the pattern seen with pseudomyxoma peritonei [5]. Right now, pseudomyxoma peritonei should be regarded as a disease of MUC2-expressing goblet cells [6]. Since 10 years ago, the standard treatment of pseudomyxoma peritonei was to remove as much of the tumor and mucus as possible in order to restore breathing and bowel functions.…”