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.
OBJECTIVE
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.


CONCLUSIONS
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.
Chakraborty
Subhankar
S
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA.
Swanson
Benjamin J
BJ
Bonthu
Neelima
N
Batra
Surinder K
SK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000175:diagnosis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003218:Condylomata Acuminata / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism; D008875:Middle Aged; D055264:Mucin-4 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
D014408:Biomarkers, Tumor; C524658:MUC4 protein, human; D055264:Mucin-4; D009363:Neoplasm Proteins