Aberrant upregulation of MUC4 mucin expression in cutaneous condyloma acuminatum and squamous cell carcinoma suggests a potential role in the diagnosis and therapy of skin diseases

被引:16
作者
Chakraborty, Subhankar
Swanson, Benjamin J.
Bonthu, Neelima
Batra, Surinder K. [1 ,2 ]
机构
[1] Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA
[2] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA
基金
美国国家卫生研究院;
关键词
PANCREATIC-CANCER; PROGNOSTIC-FACTOR; ADENOCARCINOMA; INFLAMMATION; GENES;
D O I
10.1136/jcp.2010.076125
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Aim Mucins comprise a family of high-molecular-weight glycoproteins. MUC4, a large transmembrane mucin, has recently emerged as a novel marker for diagnosis, prognosis and therapy in several malignancies. However, its role in skin pathologies remains unknown. The aim of this study was to analyse the expression of MUC4 in cutaneous pathologies by immunohistochemistry for potential diagnostic, prognostic and therapeutic applications. Methods A total of 330 tissue spots representing the normal skin, and benign and malignant cutaneous diseases, were analysed after staining with the monoclonal antibody to human MUC4 (clone 8G7). Results While the normal epidermis showed a negative to weak-positive expression of MUC4, its expression was significantly upregulated in squamous cell carcinomas (SCCs) where the intensity of staining correlated negatively with tumour grade and positively with age. A moderately strong MUC4 expression was also noted in 2/20 cancer adjacent normal skin and 2/21 chronically inflamed skin tissues, while 10/19 cases of vulval condyloma acuminate, 3/12 of vulval hyperplasia and 2 cases of verruca vulgaris also showed strong MUC4 positivity. Malignant melanoma, basal cell carcinoma and cutaneous cysts were negative. Conclusion The results indicate that MUC4 expression is aberrantly upregulated in cutaneous SCCs, vulval condylomas and verruca vulgaris. Further, it appears that MUC4 expression in the skin may be modulated by chronic inflammation and the presence of an adjacent cutaneous malignancy in certain cases. These observations suggest a novel role for MUC4 mucin in the pathogenesis of cutaneous SCC and a possible application as a diagnostic and/or prognostic marker in cutaneous pathologies.
引用
收藏
页码:579 / 584
页数:6
相关论文
共 29 条
[11]   Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis [J].
Ganguly, Niladri ;
Parihar, Suraj P. .
JOURNAL OF BIOSCIENCES, 2009, 34 (01) :113-123
[12]   EPITHELIAL MARKERS IN PRIMARY SKIN-CANCER - AN IMMUNOPEROXIDASE STUDY OF THE DISTRIBUTION OF EPITHELIAL MEMBRANE ANTIGEN (EMA) AND CARCINOEMBRYONIC ANTIGEN (CEA) IN 65 PRIMARY SKIN CARCINOMAS [J].
HEYDERMAN, E ;
GRAHAM, RM ;
CHAPMAN, DV ;
RICHARDSON, TC ;
MCKEE, PH .
HISTOPATHOLOGY, 1984, 8 (03) :423-434
[13]   MUC genes are differently expressed during onset,and maintenance of inflammation in dextran sodium sulfate-treated mice [J].
Hoebler, C ;
Gaudier, E ;
De Coppet, P ;
Rival, M ;
Cherbut, C .
DIGESTIVE DISEASES AND SCIENCES, 2006, 51 (02) :381-389
[14]   Genome-wide transcriptional profiling in human squamous cell carcinoma of the skin identifies unique tumor-associated signatures [J].
Kathpalia, Vinnie P. ;
Mussak, Erich N. ;
Chow, Selwyn S. ;
Lam, Phillip H. ;
Skelley, Nathan ;
Time, Michael ;
Markelewicz, Robert J., Jr. ;
Kanduc, Darja ;
Lomas, Lucy ;
Xiang, Zhaoying ;
Sinha, Animesh A. .
JOURNAL OF DERMATOLOGY, 2006, 33 (05) :309-318
[15]  
Lever WF, 2005, LEVERS HISTOPATHOLOG
[16]   Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia [J].
Moniaux, N. ;
Chakraborty, S. ;
Yalniz, M. ;
Gonzalez, J. ;
Shostrom, V. K. ;
Standop, J. ;
Lele, S. M. ;
Ouellette, M. ;
Pour, P. M. ;
Sasson, A. R. ;
Brand, R. E. ;
Hollingsworth, M. A. ;
Jain, M. ;
Batra, S. K. .
BRITISH JOURNAL OF CANCER, 2008, 98 (09) :1540-1547
[17]   Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans [J].
Moniaux, N ;
Varshney, GC ;
Chauhan, SC ;
Copin, MC ;
Jain, M ;
Wittel, UA ;
Andrianifahanana, M ;
Aubert, JP ;
Batra, SK .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2004, 52 (02) :253-261
[18]   Upregulation of MUC4 in Cervical Squamous Cell Carcinoma: Pathologic Significance [J].
Munro, Elizabeth G. ;
Jain, Maneesh ;
Oliva, Esther ;
Kamal, Neel ;
Lele, Subodh M. ;
Lynch, Maureen P. ;
Guo, Lankai ;
Fu, Kai ;
Sharma, Poonam ;
Remmenga, Steve ;
Growdon, Whitfield B. ;
Davis, John S. ;
Rueda, Bo R. ;
Batra, Surinder K. .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, 2009, 28 (02) :127-133
[19]   Epithelial inflammation response induced by Shigella flexneri depends on mucin gene expression [J].
Nutten, S ;
Sansonetti, P ;
Huet, G ;
Bourdon-Bisiaux, C ;
Meresse, B ;
Colombel, JF ;
Desreumaux, P .
MICROBES AND INFECTION, 2002, 4 (11) :1121-1124
[20]  
Park HU., 2003, Pancreas, V26, P48