Mucinous tumors of the vermiform appendix and ovary, and pseudomyxoma peritonei: Histogenetic implications of cytokeratin 7 expression

Guerrieri, Claudio; Frånlund, B.; Fristedt, Staffan; Gillooley, John; Boeryd, B

doi:10.1016/s0046-8177(97)90057-5

Cited by 84 publications

(40 citation statements)

References 16 publications

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“…6 -10 Because of the frequency of ovarian involvement and the high female/male ratio of pseudomyxoma peritonei the physician most often caring for the patient was the gynecologist. Recent studies of cytokeratin immunostaining patterns, 33,34 clonality studies with loss of heterozygosity, 35 and molecular studies of Ki-ras mutations 12,35 have all supported the conclusion that pseudomyxoma peritonei usually takes origin from the appendix and not the ovary. Our findings with respect to MUC2 expression would also support this same conclusion.…”

Section: Discussionmentioning

confidence: 96%

Pseudomyxoma Peritonei Is a Disease of MUC2-Expressing Goblet Cells

O'Connell

Tomlinson

Roberts

et al. 2002

The American Journal of Pathology

147

105

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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.

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Section: Discussionmentioning

confidence: 96%

Pseudomyxoma Peritonei Is a Disease of MUC2-Expressing Goblet Cells

O'Connell

Tomlinson

Roberts

et al. 2002

The American Journal of Pathology

147

105

View full text Add to dashboard Cite

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“…In exceptionally rare cases other sites have been reported to be the primary sites, such as the colon, common bile duct, pancreas and breast [20][21][22] . There is a growing body of evidence, based on morphological, immunohistochemical and genetic studies, suggesting that the primary site of origin is the appendix in majority of the cases [23][24][25][26][27] . The most popular model explaining tumor progression advocates that an initial neoplastic process (such as a mucinous adenoma) produces mucin continuously inside the appendiceal lumen, leading to obstruction and distension of this structure.…”

Section: Dissemination From the Primary Tumormentioning

confidence: 99%

Pathophysiology and biology of peritoneal carcinomatosis

Kusamura¹

2010

WJGO

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Peritoneal carcinomatosis represents a devastating form of cancer progression with a very poor prognosis. Its complex pathogenesis is represented by a dynamic process comprising several steps. To the best of our knowledge pathogenesis can be partly explained by 3 major molecular pathways: (1) dissemination from the primary tumor; (2) primary tumor of peritoneum; and (3) independent origins of the primary tumor and peritoneal implants. These are not mutually exclusive and combinations of different mechanisms could occur inside a single case. There are still several aspects which need explanation by future studies. A comprehensive understanding of molecular events involved in peritoneal carcinomatosis is of paramount importance and should be systematically pursued not only to identify novel strategies for the prevention of the condition, but also to obtain therapeutic advances, through the identification of surrogate markers of prognosis and development of future molecular targeted therapies.

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“…In classic cases over 90% of the globular masses are mucin by volume. The syndrome in the past was considered to arise either from primary appendiceal or ovarian mucinous tumors (6 -10) but recent evidence has favored an appendiceal origin (11)(12)(13)(14)(15)(16)(17)(18)(19). It has been recently demonstrated that "traditional pseudomyxoma peritonei" includes three pathologically, surgically, and prognostically distinctive types of tumors with varying degrees of malignant transformation.…”

mentioning

confidence: 99%

MUC2 Is a Molecular Marker for Pseudomyxoma Peritonei

2002

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Pseudomyxoma peritonei, a syndrome first described by 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 much past interest in the syndrome has focused on the question of whether the disease arises from primary appendiceal or ovarian mucinous tumors of varying malignant potential, the accumulation of extracellular mucin with its resulting obstruction of abdominal viscera and adhesion formation is one major cause of this disease's morbidity and mortality irrespective of the origin or transformed status of the epithelium secreting it. Because of this and because of the recent discovery and cloning of a series of specific mucin genes responsible for mucin secretion and extracellular deposition, we decided to analyze cases of pseudomyxoma peritonei with specific mucin cDNAs and corresponding antibodies to identify a characteristic marker for this disease which ultimately might be targeted therapeutically. Our study specifically investigated MUC2 and MUC5AC because these two mucins possessed the physicochemical property of being gel-forming, a property exhibited by pseudomyxoma peritonei grossly. Expression of MUC2 and MUC5AC in pseudomyxoma peritonei and in accompanying and nonaccompanying appendiceal and ovarian mucinous neoplasms were analyzed by in situ hybridization, immunocytochemistry and digital image analysis. A striking overexpression of both MUC2 and MUC5AC was observed in nearly all cases of pseudomyxoma peritonei of unknown and appendiceal origin. In these cases, however, MUC2 gene expression was more prominent. The mucin:cell ratio averaged 10 to 1 in these cases. The primary ovarian mucinous tumors, some of which exhibited pseudomyxoma ovarii and/or peritoneal implants but not classic pseudomyxoma peritonei, in contrast, expressed only MUC5AC and gave rise to implants where the mucin:cell ratio averaged only 1 to 1. MUC2 overexpression then supported an intestinal rather than ovarian origin for true pseudomyxoma peritonei, irrespective of whether an appendiceal primary was documented. In all cases studied, the fidelity of MUC2 and MUC5AC expression held irrespective of the degree of malignant transformation which was present. MUC2 is therefore a reliable molecular marker for pseudomyxoma peritonei.

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Mucinous tumors of the vermiform appendix and ovary, and pseudomyxoma peritonei: Histogenetic implications of cytokeratin 7 expression

Cited by 84 publications

References 16 publications

Pseudomyxoma Peritonei Is a Disease of MUC2-Expressing Goblet Cells

Pseudomyxoma Peritonei Is a Disease of MUC2-Expressing Goblet Cells

Pathophysiology and biology of peritoneal carcinomatosis

MUC2 Is a Molecular Marker for Pseudomyxoma Peritonei

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