Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours

Dong, Ying; Walsh, Michael D.; Cummings, Margaret C.; Wright, Robert F.; Khoo, S. K.; Parsons, Peter G.; McGuckin, Michael A.

doi:10.1002/(sici)1096-9896(199711)183:3<311::aid-path917>3.3.co;2-u

Cited by 34 publications

(47 citation statements)

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“…In the ovary, the colorectum, and breast, the mucinous phenotype was shown to express the glycoprotein MUC2, but not MUC1 (8,29). In their study on colorectal carcinomas, Biemer-Hüttmann et al (30) found a strong association between MSI and mucinous tumors positive for MUC2 and MUC5AC, supporting the hypothesis of a special pathway of carcinogenesis for mucinous carcinomas in general (8,31).…”

Section: Discussionmentioning

confidence: 92%

Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

et al. 2003

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Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual ductal adenocarcinomas in their mucin expression profile and share with many extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous carcinomas are frequently associated with mutations of the DNA mismatch repair genes, causing them to exhibit the so-called mutator phenotype, we decided to investigate whether MNCCs of the pancreas are characterized by microsatellite instability (MSI). Twelve carcinomas with a mucinous phenotype (8 mucinous noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an invasive muconodular component, and 1 ductal adenocarcinoma with an extensive mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were analyzed. MSI was diagnosed in case a novel allele was found, compared with the normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas tested exhibited nuclear expression of mismatch repair gene products, except for one MNCC that also showed MSI at the molecular level. The data suggest that pancreatic carcinomas with a mucinous phenotype (MUC2؉/MUC1؊) do not appear to normally exhibit mutations in the mismatch repair genes and therefore differ in their carcinogenesis from those in other organs.

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Section: Discussionmentioning

confidence: 92%

Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

et al. 2003

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“…3,18,22 MUC16/CA125 is the most thoroughly investigated biomarker in ovarian carcinoma and is currently in use for disease diagnosis. [2][3][4] In earlier studies, MUC4 expression in ovarian carcinoma was also examined at the transcript level using Northern blot and in situ hybridization analyses.…”

Section: Discussionmentioning

confidence: 99%

“…MUC1 is a transmembrane mucin that is overexpressed in ovarian cancer and has been shown to influence the metastatic ability of ovarian carcinoma. 18 Currently, it is also being explored as a target for antibodymediated tumor therapy. 19,20 MUC4, a high molecular weight membrane-bound mucin is aberrantly expressed in several types of carcinomas.…”

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confidence: 99%

Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)

et al. 2006

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Mucins are being implicated in diagnosis, prognosis, and as therapeutic targets due to their aberrant expression in a variety of carcinomas. Here, we have analyzed the expression of MUC4 and have compared its potential usefulness in early detection and prognosis of ovarian carcinoma alone and in combination with other mucin antigens, MUC1 and MUC16. Clinical significance of the differential mucin expression was evaluated by grouping the tumor samples in early (stage I and II) and advanced (stage III and IV) stage cases and histological subtypes (serous, mucinous, endometrioid and clear cell). Correlation of these mucins with patient's survival (n ¼ 63) was determined by Kaplan-Meier analysis in order to predict their prognostic value. MUC4 showed significant overexpression in tumor cases (Po0.0001) with highest incidence (92.0%) among all three mucins. A significant overexpression of MUC1 (Po0.018) and MUC16 (Po0.0001) was also observed in 83.0 and 79.0% of tumor samples, respectively. Notably, MUC4 expression was significantly higher (Pr0.004) compared to both MUC1 and MUC16 in early-stage ovarian tumor samples with 100% incidence. In advanced stage ovarian tumors, all the mucins displayed overall comparable expression, nonetheless, MUC4 had highest prevalence (88.0%) compared to MUC1 (84.0%) and MUC16 (81.0%). A combined panel of MUC4 with MUC16 detected 100% of the late-stage tumor cases without compromising the specificity. Among histological subtypes, only MUC4 displayed 100% (n ¼ 5) sensitivity in mucinous ovarian tumors, while MUC1 and MUC16 detected 40 and 20% cases, respectively. The expression of MUC4, however, did not significantly correlate with the survival of the ovarian cancer patient, while a significant correlation of MUC16 with poor prognosis was observed. In conclusion, our study demonstrates that MUC4 could be a potential candidate marker for early diagnosis of epithelial ovarian carcinoma and can be utilized in combination with MUC16 to achieve greater sensitivity for the detection of late-stage tumors.

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“…17 The vast majority of ovarian tumors have also been reported to overexpress MUC1, [18][19][20][21] while it is weakly or not at all expressed by normal mesothelial cells. 29 Following the success of the CMV/ NIS construct, we proceeded to use Ad/MUC1/NIS to provide transcriptional targeting to the tumors and minimize potential effects on surrounding normal cells.…”

Section: Discussionmentioning

confidence: 99%

“…12 We have previously reported the successful use of the MUC1 promoter to drive NIS expression for radioiodide imaging and therapy of breast cancer cells. 17 MUC1 overexpression has also been reported in the majority of ovarian tumors, [18][19][20][21] and so this construct has potential for application in this tumor model. This study describes the introduction of NIS expression into ovarian tumor cells both in vitro and in vivo, followed by 123 I imaging and 131 I therapy.…”

Section: Introductionmentioning

confidence: 99%

Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

et al. 2005

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Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours

Cited by 34 publications

References 0 publications

Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)

Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

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