Second-Generation Monoclonal Antibodies to Intestinal MUC2 Peptide Reactive With Colon Cancer

Xing, Pei‐Xiang; Prenzoska, Julie; Layton, Guy T.; Devine, Peter L.; McKenzie, Ian F. C.

doi:10.1093/jnci/84.9.699

Cited by 80 publications

(38 citation statements)

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“…Our study also focused on MUC2 and MUC5AC because recent studies had observed differential expression of these 2 mucins in gastrointestinal v ovarian neoplasms (25). MUC2 had been known to be expressed in both the gastrointestinal tract as well as the bronchus (32)(33)(34)(35). MUC5AC had also been observed to be expressed in both of these sites as well as the endocervix and endometrium (36).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

MUC2 Is a Molecular Marker for Pseudomyxoma Peritonei

2002

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“…33 All three antimucin antibodies are specific for their respective mucins and are not believed to crossreact with other mucins. [31][32][33] Neutrophils were detected using an antineutrophil elastase antibody 34 (Dako, Cambridge, UK). Isotype matched antibody controls were routinely used and were negative in all cases.…”

Section: Bronchoscopy and Immunostainingmentioning

confidence: 99%

Expression of ErbB receptors and mucins in the airways of long term current smokers

O’Donnell

2004

Thorax

124

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Background: Airway epithelial goblet cell hyperplasia is known to occur in chronic smokers. Although the epidermal growth factor receptor has been implicated in this process, neither ErbB receptor expression nor the mucosecretory phenotype of the epithelium have been characterised in current smokers. Methods: Bronchial biopsies obtained from non-smokers (n = 10) and current smokers, with or without chronic obstructive pulmonary disease (n = 51), were examined immunohistochemically to measure the expression of epidermal growth factor receptor, ErbB2, ErbB3, ErbB4 and mucin subtypes (MUC2, MUC5AC and MUC5B) in the bronchial epithelium. The results were correlated with neutrophil counts measured in the airway wall and induced sputum. Results: Epidermal growth factor receptor, ErbB3 and MUC5AC expression, in addition to PAS staining, were significantly increased in all smokers compared with non-smokers, irrespective of the presence of chronic obstructive pulmonary disease. MUC5AC expression was significantly associated with both PAS staining and ErbB3 expression; no correlation was observed between either mucin or ErbB receptor expression and neutrophil counts. Conclusions:The results suggest that long term current smoking induces enhanced epidermal growth factor receptor, ErbB3, and MUC5AC expression in vivo; these increases are not associated with the presence of neutrophilic inflammation. ErbB receptors may contribute to epithelial responses to cigarette smoke.

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“…Immunohistochemistry using tandem-repeat-spccific antibodies has been performed in several previous studies [33,41,42]; how ever. the immunostaining obtained with these antibodies must be interpreted cautiously.…”

Section: Comparison With Colon and Breast Adenocarcinomasmentioning

confidence: 99%

Membrane-Bound (MUC1) and Secretory (MUC2, MUC3, and MUC4) Mucin Gene Expression in Human Lung Cancer

et al. 1996

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Abnormalities of mucin-type glycoproteins have been described in lung cancers, but their molecular basis is unknown. In this study, mucin-core-peptide-specific antibodies and cDNA probes were used to determine the relative expression of mucin genes corresponding to one membrane-bound mucin (MUC1), two intestinal mucins (MUC2 and MUC3), and one tracheobronchial mucin (MUC4) in normal (nonneoplastic) lung, and in lung neoplasms. Normal lung tissues exhibited a distinct pattern of mucin gene expression, with high levels of MUC1 and MUC4 mRNA and low to absent levels of MUC2 and MUC3 mucin immunoreactivity and mRNA. In contrast, lung adenocarcinomas, especially well-differentiated cancers, exhibited increased MUC1, MUC3, and MUC4 mRNA levels. Lung squamous-cell, adenosquamous, and large-cell carcinomas were characterized by increased levels of MUC4 mucin only. We conclude that the expression of one membrane-bound and several secretory-type mucins is independently regulated and markedly altered in lung neoplasms. The frequent occurrence of increased MUC4 transcripts in a variety of non-small-cell lung cancers indicates the potential importance of this type of mucin in lung cancer biology.

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Second-Generation Monoclonal Antibodies to Intestinal MUC2 Peptide Reactive With Colon Cancer

Abstract: Anti-MUC2 peptide antibodies appear to be relatively tissue specific and represent a new method of producing antitumor antibodies.

Cited by 80 publications

References 0 publications

MUC2 Is a Molecular Marker for Pseudomyxoma Peritonei

MUC2 Is a Molecular Marker for Pseudomyxoma Peritonei

Expression of ErbB receptors and mucins in the airways of long term current smokers

Membrane-Bound (MUC1) and Secretory (MUC2, MUC3, and MUC4) Mucin Gene Expression in Human Lung Cancer

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