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

Nguyen, Phuong L.; Niehans, Gloria A.; Cherwitz, David L.; Kim, Young S.; Ho, Samuel B.

doi:10.1159/000217980

Cited by 64 publications

(62 citation statements)

References 23 publications

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“…Some previous studies have reported that MUC4 may have a prognostic value in cancer including breast cancer. 28,29 However, we did not find any associations between MUC4 and any of the clinicopathological parameters or patients outcome in our series. The functions that have previously been suggested as possible tumour precipitating factors 39,40 have not been studied individually in this study, and more work still needs to be carried out to determine the role of this mucin in breast cancer.…”

Section: Discussioncontrasting

confidence: 79%

“…28 The deregulation of MUC4 may be a factor for tumour progression and its altered expression has been found in a number of carcinomas. 29,30 In this study, we have assessed the expression profiles of different mucins and evaluate their prognostic significance in a large and well-characterized series of breast cancer, prepared as tissue microarrays (TMA), using immunohistochemistry.…”

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confidence: 99%

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Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer

et al. 2005

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Mucins are a large family of glycoproteins expressed by many epithelial cells and their malignant counterparts. Much interest has been focused on expression of its members in breast cancer because of their potential role as prognostic indicators and their involvement in cancer therapy. We have examined 1447 cases of invasive breast carcinoma with a long-term follow-up, using tissue microarray (TMA) technology and immunohistochemistry to evaluate the expression profiles of several mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and to assess their prognostic value. We detected MUC1 expression in 91% of tumours. MUC1 overexpression was associated with a lower grade, smaller tumour size, a higher oestrogen receptor (ER)-positive phenotype and absence of both regional recurrence and distance metastasis. The subcellular localization but not the level of expression had a prognostic value in predicting outcome. The aberrant cytoplasmic and membranous localization of MUC1 was associated with poor outcome compared with apical localization, which is the normal physiological site of expression. MUC2 expression was noticed in only 8.3% of all cases and was restricted to the cytoplasm of the tumour cells. An inverse trend was identified between MUC2 expression and lymph node stage and vascular invasion status. On excluding cases of mucinous carcinoma from the analysis, the inverse association with vascular invasion was still defined and in addition an inverse association with ER status emerged. MUC3 expression was detected in 91% of cases and its expression was associated with increased local recurrence, and lymph node stage. The membranous expression of MUC3 was found to be a potentially poor prognostic feature, with higher grade and poorer Nottingham Prognostic Index (NPI), and negative ER expression. MUC4, MUC5AC and MUC6 were expressed in 95, 37 and 20% of cases, respectively. Apart from an association between MUC4 expression and tumour grade and between MUC6 and ER-negative tumours, no other associations with any clinicopathological variables were found. Apart from the higher expression of MUC2 and MUC6 in mucinous carcinomas, no association was found between the expression of different mucins and tumour type. No association between the level of expression of any of the studied mucins and patient outcomes has been identified. In conclusion, most breast carcinomas express MUC1, MUC3 and MUC4. Among the various mucins expressed in breast cancer, MUC1 and MUC3 are potential prognostic indicators, MUC1 having the strongest relationship with patient outcome.

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Section: Discussioncontrasting

confidence: 79%

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confidence: 99%

Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer

et al. 2005

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“…34 MUC4 mRNA expression has also been described in lung carcinomas by Northern blot analysis and RT-PCR. [37][38][39] In this study, we confirmed the frequent expression of both MUC4 protein and transcripts in lung adenocarcinomas.…”

Section: Discussionsupporting

confidence: 74%

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

et al. 2004

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The distinction between pleural malignant mesothelioma and pleural infiltration by adenocarcinomas has complex therapeutic and medicolegal implications. Although the panel of adenocarcinoma-associated antibodies and one or two mesothelioma markers is useful in this purpose, most of these antibodies are not totally specific. We determined the diagnostic value of MUC4 immunostaining in this issue. MUC4 gene expression was also studied by in situ hybridization and RT-PCR. MUC4 is a membrane-bound mucin that has been suggested to be implicated in malignant progression in humans and rats. The MUC4 gene is expressed in various normal epithelial tissues of endodermic origin and carcinomas. In the respiratory tract, MUC4 transcripts have been detected in normal respiratory epithelium and lung carcinomas. MUC4 protein was expressed in 32 of 35 (91.4%) lung adenocarcinomas on paraffin-embedded tissue. None of the 41 malignant mesotheliomas nor the 32 cases of benign mesothelial cells expressed MUC4 at the protein and mRNA levels. We conclude that MUC4 is a very specific (100%) and sensitive (91.4%) marker of lung adenocarcinomas on paraffin-embedded tissue that could be useful in diagnostic practice in the distinction between malignant mesothelioma and adenocarcinoma.

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“…Furthermore, in recent studies, a progressive increase in MUC4 expression has been observed in pancreatic intraepithelial neoplastic lesions (11,12), indicating its role in disease development. The up-regulation of MUC4 in several other human adenocarcinomas (13)(14)(15)(16) also indicates the potential importance of this mucin in tumor biology.…”

Section: Introductionmentioning

confidence: 97%

Inhibition of MUC4 Expression Suppresses Pancreatic Tumor Cell Growth and Metastasis

Singh¹,

Moniaux²,

Chauhan³

et al. 2004

Cancer Research

226

257

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

Cited by 64 publications

References 23 publications

Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer

Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

Inhibition of MUC4 Expression Suppresses Pancreatic Tumor Cell Growth and Metastasis

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