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

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2010 Jul 2

PMID 20591909

Citations 10

Authors

Subhankar Chakraborty

Benjamin J Swanson

Neelima Bonthu

Surinder K Batra

Affiliations

Soon will be listed here.

Abstract

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.

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References

Chaturvedi P, Singh A, Batra S . Structure, evolution, and biology of the MUC4 mucin. FASEB J. 2007; 22(4):966-81. PMC: 2835492. DOI: 10.1096/fj.07-9673rev. View

Moniaux N, Chakraborty S, Yalniz M, Gonzalez J, Shostrom V, Standop J . Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia. Br J Cancer. 2008; 98(9):1540-7. PMC: 2391106. DOI: 10.1038/sj.bjc.6604329. View

Singh A, Chauhan S, Bafna S, Johansson S, Smith L, Moniaux N . Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas. Prostate. 2005; 66(4):421-9. DOI: 10.1002/pros.20372. View

Riker A, Enkemann S, Fodstad O, Liu S, Ren S, Morris C . The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics. 2008; 1:13. PMC: 2408576. DOI: 10.1186/1755-8794-1-13. View

Ponnusamy M, Singh A, Jain M, Chakraborty S, Moniaux N, Batra S . MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cells. Br J Cancer. 2008; 99(3):520-6. PMC: 2527793. DOI: 10.1038/sj.bjc.6604517. View

Park H, Kim J, Kim G, Bae H, Crawley S, Yang S . Aberrant expression of MUC3 and MUC4 membrane-associated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasia. Pancreas. 2003; 26(3):e48-54. DOI: 10.1097/00006676-200304000-00022. View

Salasche S . Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 1999; 42(1 Pt 2):4-7. DOI: 10.1067/mjd.2000.103342. View

Senapati S, Chaturvedi P, Sharma P, Venkatraman G, Meza J, El-Rifai W . Deregulation of MUC4 in gastric adenocarcinoma: potential pathobiological implication in poorly differentiated non-signet ring cell type gastric cancer. Br J Cancer. 2008; 99(6):949-56. PMC: 2538752. DOI: 10.1038/sj.bjc.6604632. View

Bhardwaj A, Marsh Jr W, Nash J, Barbacioru C, Jones S, Frankel W . Double immunohistochemical staining with MUC4/p53 is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray-based study. Arch Pathol Lab Med. 2007; 131(4):556-62. DOI: 10.5858/2007-131-556-DISWPI. View

10.

Tsutsumida H, Goto M, Kitajima S, Kubota I, Hirotsu Y, Wakimoto J . MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma. Lung Cancer. 2006; 55(2):195-203. DOI: 10.1016/j.lungcan.2006.10.013. View

11.

Fleischer Jr A, Feldman S, Rapp S . Introduction. The magnitude of skin disease in the United States. Dermatol Clin. 2000; 18(2):xv-xxi. DOI: 10.1016/s0733-8635(05)70163-7. View

12.

Chauhan S, Singh A, Ruiz F, Johansson S, Jain M, Smith L . Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). Mod Pathol. 2006; 19(10):1386-94. DOI: 10.1038/modpathol.3800646. View

13.

Heyderman E, Graham R, Chapman D, Richardson T, McKee P . 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. Histopathology. 1984; 8(3):423-34. DOI: 10.1111/j.1365-2559.1984.tb02354.x. View

14.

Kathpalia V, Mussak E, Chow S, Lam P, Skelley N, Time M . Genome-wide transcriptional profiling in human squamous cell carcinoma of the skin identifies unique tumor-associated signatures. J Dermatol. 2006; 33(5):309-18. DOI: 10.1111/j.1346-8138.2006.00075.x. View

15.

Moniaux N, Varshney G, Chauhan S, Copin M, Jain M, Wittel U . Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans. J Histochem Cytochem. 2004; 52(2):253-61. DOI: 10.1177/002215540405200213. View

16.

Chakraborty S, Jain M, Sasson A, Batra S . MUC4 as a diagnostic marker in cancer. Expert Opin Med Diagn. 2013; 2(8):891-910. DOI: 10.1517/17530059.2.8.891. View

17.

Hoebler C, Gaudier E, de Coppet P, Rival M, Cherbut C . MUC genes are differently expressed during onset and maintenance of inflammation in dextran sodium sulfate-treated mice. Dig Dis Sci. 2006; 51(2):381-9. DOI: 10.1007/s10620-006-3142-y. View

18.

Nutten S, Sansonetti P, Huet G, Meresse B, Colombel J, Desreumaux P . Epithelial inflammation response induced by Shigella flexneri depends on mucin gene expression. Microbes Infect. 2002; 4(11):1121-4. DOI: 10.1016/s1286-4579(02)01636-2. View

19.

Alos L, Lujan B, Castillo M, Nadal A, Carreras M, Caballero M . Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands. Am J Surg Pathol. 2005; 29(6):806-13. DOI: 10.1097/01.pas.0000155856.84553.c9. View

20.

Alam M, Ratner D . Cutaneous squamous-cell carcinoma. N Engl J Med. 2001; 344(13):975-83. DOI: 10.1056/NEJM200103293441306. View