Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background : Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance. Methods : We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray. Results : We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128). Conclusions : MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.
Abstract
Background : Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance. Methods : We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray. Results : We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128). Conclusions : MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.
참고문헌 (30)
- Kelsey CR, "Local", regional recurrence following surgery for early-stage lung cancer: a 10-year experience with 975 patients, 2008, pp.26(15 Suppl), 7542~
- Liu XQ, "Detecting MUC-1 mRNA for diagnosing peripheral blood micro-metastasis in non-small cell lung cancer patients", Ai Zheng, 27, pp.1267~1270 (2008)
- Komatsu M, "Potentiation of metastasis by cell surface sialomucin complex(rat MUC4),a multifunctional anti-adhesive glycoprotein", Int J Cancer, 87, pp.480~486 (2000)
- Moniaux N, "Structural organization and classification of the human mucin genes", Front Biosci, 6, pp.D1192~D1206 (2001)
- Senapati S, "The MUC gene family:their role in the diagnosis and prognosis of gastric cancer", Histol Histopathol, 23, pp.1541~1552 (2008)
- Nakamori S, "MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma", Gastroenterology, 106, pp.353~361 (1994)
- Ho SB, "Heterogeneity of mucin gene expression in normal and neoplastic tissues", Cancer Res, 53, pp.641~651 (1993)
- Okabe S, "Clinicopathological study of mucous pooling referred to as mucinous component(MUC)in colorectal submucosal invasive carcinomas", J Med Dent Sci, 48, pp.69~78 (2001)
- Monges GM, "Differential MUC 1 expression in normal and neoplastic human pancreatic tissue:an immunohistochemical study of 60 samples", Am J Clin Pathol, 112, pp.635~640 (1999)
- Khodarev NN, "MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer", Cancer Res, 69, pp.2833~2837 (2009)
- Andrianifahanana M, "Mucin(MUC)gene expression in human pancreatic adenocarcinoma and chronic pancreatitis:a potential role of MUC4 as a tumor marker of diagnostic significance", Clin Cancer Res, 7, pp.4033~4040 (2001)
- Carraway KL, "Muc4", sialomucin complex in the mammary gland and breast cancer, 2001, pp.6, 323~337
- Shibahara H, "MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type", Hepatology, 39, pp.220~229 (2004)
- Hanaoka J, "Analysis of MUC4 mucin expression in lung carcinoma cells and its immunogenicity", Cancer, 92, pp.2148~2157 (2001)
- Travis WD, "World Health Organization classification of tumours: pathology and genet- ics of tumours of the lungs, pleura, thymus and heart" (2004), IARC Press
- Goldstraw P, "The IASLC Lung Cancer Staging Project:proposals for the revision of the TNM stage groupings in the forthcoming(seventh)edition of the TNM classification of malignant tumours", J Thorac Oncol, 2, pp.706~714 (2007)
- Seregni E, "Pattern of mucin gene expression in normal and neoplastic lung tissues", Anticancer Res, 16, pp.2209~2213 (1996)
- Maeshima A, "Mucin-producing adenocarcinoma of the lung,with special reference to goblet cell type adenocarcinoma:immunohistochemical observation and Kiras gene mutation", Pathol Int, 47, pp.454~460 (1997)
- Tsuda T, "Mucin gene expression is associated with the poor prognosis in human non-small cell lung cancer", Proc Am Assoc Cancer Res, 36, pp.214~ (1995)
- Zhao Q, "Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface", Cancer Res, 69, pp.6799~6806 (2009)
- Nogi H, "Detection of MUC1 and keratin 19 mRNAs in the bone marrow by quantitative RT-PCR predicts the risk of distant metastasis in breast cancer patients", Breast Cancer, 10, pp.74~81 (2003)
- Nitta T, "Immunohistochemical study of MUC1 mucin in premalignant oral lesions and oral squamous cell carcinoma:association with disease progression,mode of invasion,and lymph node metastasis", Cancer, 88, pp.245~254 (2000)
- Wesseling J, "A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membraneassociated mucin episialin", MUC1, 1996, pp.7, 565~577
- Wesseling J, "Episialin(MUC1)overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components", J Cell Biol, 129, pp.255~265 (1995)
- van de Wiel-van Kemenade E, "Episialin(MUC1)inhibits cytotoxic lymphocyte-target cell interaction", J Immunol, 151, pp.767~776 (1993)
- Weed DT, "MUC4 and ErbB2 expression in squamous cell carcinoma of the upper aerodigestive tract:correlation with clinical outcomes", Laryngoscope, 114, pp.1~32 (2004)
- Takao S, "Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis", Cancer, 86, pp.1966~1975 (1999)
- Weed DT, "MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma", Head Neck, 26, pp.353~364 (2004)
- Theodoropoulos G, "MUC4 involvement in ErbB2", ErbB3 phosphorylation and signaling in response to airway cell mechanical injury, 2009, pp.107, 112~122
- Ramsauer VP, "Muc4-ErbB2 complex formation and signaling in polarized CACO-2 epithelial cells indicate that Muc4 acts as an unorthodox ligand for ErbB2", Mol Biol Cell, 17, pp.2931~2941 (2006)
