MUC1 is a transmembrane mucin that has been related to tumor progression and outcome in various malignancies. However, the clinical significance in thymic epithelial tumors remains unknown. We investigated the clinical significance of MUC1 expression in thymic epithelial tumors. Fifty-five patients with thymic epithelial tumors were included in this study. Tumors sections were stained by immunohistochemistry for MUC1, vascular endothelial growth factor (VEGF), microvessel density (MVD) determined by CD34, and p53. MUC1 were expressed in 29%. The expression of MUC1 was significantly correlated with the grade of malignancy in thymic epithelial tumors. MUC1 was closely associated with VEGF, p53 and MVD, and the overexpression of MUC1 was a prognostic marker for predicting poor outcome in univariate analysis. A positive rate of MUC1 expression was 94% (16/17) in thymic carcinomas and 0% (0/5) in type B3 thymomas, demonstrating a significant difference (p < 0.0001). The expression of MUC1 was closely related to the grade of malignancy in thymic epithelial tumors. A positive expression of MUC1 was significantly associated with poor outcome in this disease. MUC1 may be useful marker for differentiating thymic carcinoma from type B3 thymoma.
MUC1 Thymic epithelial tumor Prognosis Thymic carcinoma Type B3 thymoma
This work was supported in part by Grant 21790793 (K. K) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and National Hospital Organization Policy Based Medical Services.
We thank all the staff of the Department of Pathology in Shizuoka Cancer Center for their technical assistance of immunohistochemical analysis.
Conflicts of interest statement
We, all authors, have no financial or personal relationships with other people or organizations that could inappropriately influence our work.
Engels EA, Pfeiffer RW (2003) Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer 105:546–551PubMedCrossRefGoogle Scholar
Rosai J, Sobin LH (1999) Histological typing of tumours of the thymus, International histological classification of tumours, 2nd edn. Springer, New York, pp 1–59Google Scholar
Travis WD, Brambillia E, Muller-Hermelink HK (2004) WHO classification of tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press, LyonGoogle Scholar
Gendler SJ, Lancaster CA, Taylor-Papadimitriou J et al (1990) Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem 265:15286–15293PubMedGoogle Scholar
Schroeder JA, Masril AA, Adriance MC et al (2004) MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. Oncogene 23:5739–5747PubMedCrossRefGoogle Scholar
Nagai S, Takenaka K, Sonobe M et al (2006) A novel classification of MUC1 expression is correlated with tumor differentiation and postoperative prognosis in non-small cell lung cancer. J Thorac Oncol 1:46–51PubMedCrossRefGoogle Scholar
Broadbent R, Thynne G, McKenzie IFC (1997) Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. J Clin Invest 100:2783–2792PubMedCrossRefGoogle Scholar
Woenckhaus M, Merk J, Stoehr R et al (2008) Prognostic value of FHIT, CTNNB1, and MUC1 expression in non-small cell lung cancer. Hum Pathol 39:126–136PubMedCrossRefGoogle Scholar
Masaoka A, Monden Y, Nakahara K et al (1981) Follow-up study of thymomas with special reference to their clinical stages. Cancer 48:2485–2492PubMedCrossRefGoogle Scholar
Kaira K, Endo M, Abe M et al (2010) Biologic correlation of 2-[18F]-fluoro-2-deoxy-D-glucose uptake on positron emission tomography in thymic epithelial tumors. J Clin Oncol 28:3746–3753PubMedCrossRefGoogle Scholar
Utsunomiya T, Yonezawa S, Sakamoto H et al (1998) Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients. Clin Cancer Res 4:2605–2614PubMedGoogle Scholar
Hinoda Y, Ikematsu Y, Horinouchi M et al (2003) Increased expression of MUC1 in advanced pancreatic cancer. J Gastroenterol 38:1162–1166PubMedCrossRefGoogle Scholar
Tamada S, Goto M, Nomoto M et al (2002) Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: its relationship with tumor progression and prognosis. Pathol Int 52:713–723PubMedCrossRefGoogle Scholar
Kawamoto T, Shoda J, Miyahara N et al (2004) Expression of MUC1 recognized by a monoclonal antibody MY.1E12 is a useful biomarker for tumor aggressiveness of carcinoma of the gallbladder. Clin Exp Metastasis 21:353–362PubMedCrossRefGoogle Scholar
Feng H, Ghazizadeh M, Konishi H et al (2002) Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas. Jpn J Clin Oncol 32:525–529PubMedCrossRefGoogle Scholar
Sivridis E, Giatromanolaki A, Koukourakis MI et al (2002) Patterns of episialin/MUC1 expression in endometrial carcinomas and prognostic relevance. Histopathology 40:92–100PubMedCrossRefGoogle Scholar
Baldus SE, Monig SP, Huxel S et al (2004) MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res 10:2790–2796PubMedCrossRefGoogle Scholar
Kirschenbaum A, Itzkowitz SH, Wang JP et al (1999) MUC1 expression in prostate carcinoma: correlation with grade and stage. Mol Urol 3:163–168PubMedGoogle Scholar
Kojika M, Ishii G, Yoshida J et al (2010) Immunohistochemical differential diagnosis between thymic carcinoma and type B3 thymoma: diagnostic utility of hypoxic marker, GLUT1, in thymic epithelial neoplasms. Modern Pathol 22:1341–1350CrossRefGoogle Scholar
Kontani K, Taguchi O, Ozaki Y et al (2003) Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucins. Int J Mol Med 12:493–502PubMedGoogle Scholar
Kufe DW (2009) Functional targeting of the MUC1 oncogene in human cancers. Cancer Biol Ther 8:1197–1203PubMedGoogle Scholar