Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA.
J Clin Pathol. 2010 Jul;63(7):579-84. doi: 10.1136/jcp.2010.076125.
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.
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).
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.
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.
黏蛋白是一类高分子量糖蛋白。MUC4 是一种大型跨膜黏蛋白,最近已成为几种恶性肿瘤诊断、预后和治疗的新型标志物。然而,其在皮肤病变中的作用尚不清楚。本研究旨在通过免疫组织化学分析 MUC4 在皮肤病变中的表达,以期为皮肤病变的诊断、预后和治疗提供新的标志物。
对 330 个组织点进行分析,这些组织点代表正常皮肤、良性和恶性皮肤疾病,并用抗人 MUC4 单克隆抗体(克隆 8G7)进行染色。
正常表皮 MUC4 表达为阴性至弱阳性,而在鳞状细胞癌(SCC)中表达明显上调,染色强度与肿瘤分级呈负相关,与年龄呈正相关。在 20 例癌旁正常皮肤和 21 例慢性炎症皮肤组织中也观察到中度强 MUC4 表达,而在 19 例外阴尖锐湿疣、12 例外阴增生和 2 例寻常疣中也观察到强 MUC4 阳性。恶性黑色素瘤、基底细胞癌和皮肤囊肿均为阴性。
结果表明,MUC4 在皮肤 SCC、外阴尖锐湿疣和寻常疣中表达异常上调。此外,在某些情况下,皮肤中 MUC4 的表达似乎可受慢性炎症和邻近皮肤恶性肿瘤的调节。这些观察结果提示 MUC4 黏蛋白在皮肤 SCC 的发病机制中具有新的作用,并可能作为皮肤病变的诊断和/或预后标志物。