Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung.

We examined the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemical staining in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma with mixed subtypes (MX) to study the association between the biologic features of adenocarcinoma of the lung and mucin expression. MUC1 expression was decreased significantly in the progression from AAH through BAC to MX, while the levels of expression of MUC2, MUC5AC, MUC6, and depolarized MUC1 were increased significantly. Alterations in the expression of depolarized MUC1, MUC5AC, and MUC6 were correlated significantly with p53 gene abnormalities. Depolarized MUC1 expression also was correlated significantly with Ki-67 expression, and down-regulation of MUC1 expression and up-regulation of MUC6 expression were correlated significantly with tumor size. Our results suggest that the expression of these mucins might be associated with the progression of adenocarcinoma of the lung.

[1]  H. Popper,et al.  Atypical Adenomatous Hyperplasia of the Lung: A Probable Forerunner in the Development of Adenocarcinoma of the Lung , 2001, Modern Pathology.

[2]  S Sone,et al.  High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT. , 2001, AJR. American journal of roentgenology.

[3]  A. Sonnenberg,et al.  Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components , 1995, The Journal of cell biology.

[4]  A. Hölscher,et al.  Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl‐Lewisa and sialyl‐Lewisx antigens in colorectal adenocarcinoma , 2002, Histopathology.

[5]  N. Kohno,et al.  Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines. , 1998, Cancer research.

[6]  R. Hruban,et al.  p53 alterations in atypical alveolar hyperplasia of the human lung. , 1998, Human pathology.

[7]  Y. Nakanuma,et al.  Expression of MUC2, MUC5AC and MUC6 apomucins in carcinoma, dysplasia and non‐dysplastic epithelia of the gallbladder , 1999, Pathology international.

[8]  I. van Seuningen,et al.  Transcriptional regulation of the 11p15 mucin genes. Towards new biological tools in human therapy, in inflammatory diseases and cancer? , 2001, Frontiers in bioscience : a journal and virtual library.

[9]  S. Chae,et al.  Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in colorectal carcinomas. , 2002, Journal of Korean medical science.

[10]  Y. Shimosato,et al.  Histological Typing of Lung and Pleural Tumours , 1999, World Health Organization.

[11]  Takaaki Ito,et al.  Reduced expression of p27/Kip1 is associated with the development of pulmonary adenocarcinoma , 2000, The Journal of pathology.

[12]  Y. Takeshima,et al.  Correlation between genetic alterations and histopathological subtypes in bronchiolo‐alveolar carcinoma and atypical adenomatous hyperplasia of the lung , 2000, Pathology international.

[13]  A. Harris,et al.  MUC1 (episialin) expression in non-small cell lung cancer is independent of EGFR and c-erbB-2 expression and correlates with poor survival in node positive patients. , 1998, Journal of clinical pathology.

[14]  J. Jass,et al.  Significance of MUC1 and MUC2 mucin expression in colorectal cancer. , 1996, Journal of clinical pathology.

[15]  H. Stein,et al.  MUC2 gene suppression in human colorectal carcinomas and their metastases: in vitro evidence of the modulatory role of DNA methylation. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[16]  M. Copin,et al.  Induction of MUC2 and MUC5AC Mucins by Factors of the Epidermal Growth Factor (EGF) Family Is Mediated by EGF Receptor/Ras/Raf/Extracellular Signal-regulated Kinase Cascade and Sp1* , 2002, The Journal of Biological Chemistry.

[17]  K. Eguchi,et al.  Expression of eukaryotic initiation factor 4E in atypical adenomatous hyperplasia and adenocarcinoma of the human peripheral lung. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  C. Melief,et al.  Episialin (MUC1) inhibits cytotoxic lymphocyte-target cell interaction. , 1993, Journal of immunology.

[19]  Y. Nishiwaki,et al.  Monoclonality of atypical adenomatous hyperplasia of the lung. , 1999, The American journal of pathology.

[20]  D Hoffmann,et al.  Smoking and lung cancer: scientific challenges and opportunities. , 1994, Cancer research.

[21]  K. Imai,et al.  Effect of MUC1 Mucin, an Anti‐adhesion Molecule, on Tumor Cell Growth , 1996, Japanese journal of cancer research : Gann.

[22]  M. Pasdar,et al.  The importance of MUC1 cellular localization in patients with breast carcinoma , 2001, Cancer.

[23]  S. Daya.  Fisher exact test , 2002 .

[24]  R. Hruban,et al.  K-ras oncogene activation in atypical alveolar hyperplasias of the human lung. , 1996, Cancer research.

[25]  S. Steinberg,et al.  MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis. , 1998, Cancer research.

[26]  A. Marchetti,et al.  BRONCHIOLOALVEOLAR LUNG CARCINOMAS: K‐ras MUTATIONS ARE CONSTANT EVENTS IN THE MUCINOUS SUBTYPE , 1996, The Journal of pathology.

[27]  S. Crawley,et al.  Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. , 2002, Gastroenterology.

[28]  S. Tsuchida,et al.  Transcriptional Activation of the MUC2 Gene by p53* , 2002, The Journal of Biological Chemistry.

[29]  K. Sugimachi,et al.  Lung adenocarcinoma with bronchioloalveolar carcinoma component is frequently associated with foci of high-grade atypical adenomatous hyperplasia. , 2002, American journal of clinical pathology.

[30]  S. Barsky,et al.  Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features , 1994, Cancer.

[31]  G. Pruneri,et al.  Depolarized expression of episialin (EMA, MUC1) in lung adenocarcinoma is associated with tumor progression. , 1998, Anticancer research.

[32]  J. Lloreta,et al.  Mucins as differentiation markers in bronchial epithelium. Squamous cell carcinoma and adenocarcinoma display similar expression patterns. , 2001, American journal of respiratory cell and molecular biology.

[33]  C. A. Carraway,et al.  Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27kip, but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways , 2002, Oncogene.