The Distribution, Expression And Value Of CK5/6, CK14, CD44v6 And OPN In Extramammary Paget's Disease

Extramammary Paget's disease(EMPD) which is also said extramammary eczematous carcinoma. Crocker,in 1889,described the first patient with extramammary Paget's disease. The disease is a special type of rare skin malignant neoplasm which is frequently taken place in the parts of apocrine gland bearing skin. It's characterized by eczematous lesions in clinical and Paget's cells in histological.The histogenesis of EMPD has long been a subject of controversy. Cytokeratin(CK) is the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity,if's changed with express different in epithelial cells,but the specific group of CK remained keep relatively invariability,the neoplasm which has epithelial structure differentiation characteristics may keep relevant express of CK.CD44 is an integral membrane glycoprotein.CD44v6 is a widely distributed cell adhesion molecule that is the major cell surface receptor for hyaluronic acid and mediates diverse functions.Osteopontin(OPN) is a phosphoprotein which relate to malignant transformation,its high expression in tumor relate with increased tumor cells metastatic potential.OPN is able to engage several receptors, including integrins and CD44v6 variants, and thus may stimulate diverse signaling pathways and influence cellular events that,in turn,favor tumorigenesis and metastasis.Objective Up to date there's no report about expression or significance of CK5/6,CK14,CD44v6 and OPN in Extramammary Paget's disease in literature.In this study,it's our objective that the results may provide a novel insight and means in clinical diagnosis and prognosis for EMPD.Methods Two-step immunohistochemistry technology was used to detect the expression of CK5/6,CK14,CD44v6 and OPN in 34 cases of EMPD and 20 cases of normal skin tissues from skin surgery department.Laboratory data were analyzed statistically together with the related clinical-pathological data.Results CK5/6 and CK14 mainly diffused express in full-thickness epidermis in EMPD patients, and the positive rates were 91.17% and 88.24% respectively. The positive expressed in the epidermis is diffuse, nests, scattered,and negative express in tumor cells. The expression of CK5/6 and CK14 apparently in EMPD and that in normal skin tissues has statistical significance (P<0.005). The positive rates of OPN and CD44v6 expression in EMPD were 70.59% and 82.35% respectively. The expression of OPN and CD44v6 were apparently higher in EMPD than that in normal skin tissues (P<0.05). The positive rates of OPN and CD44v6 were associated with lymph node metastasis (P<0.05).There was a positive correlation between OPN and CD44v6 (r=0.58, P<0.05)Conclusion CK5/6 and CK14 mainly diffused express in full-thickness epidermis in EMPD patients, and negative express in tumor cells.In the normal skin CK5/6 and CK 14 only diffused express in basal layer,and distribut linear. It is speculated that along with the upward differentiation of basal cell,CK5 and CK14 changed CK1 and CK10,the influence of tumor cells of EMPD migh prevent the transformation.Overexpression of OPN and CD44v6 may contribute to the pathogenesis of EMPD.In EMPD,OPN is able to engage several receptors, including integrins and CD44v6 variants, and thus may stimulate diverse signaling pathways and influence cellular events that,in turn,favor tumorigenesis and metastasis. The high expression of CD44v6 and OPN in EMPD and the expression of CD44v6 and OPN was not significantly correlated with age,gender. However,they are correlated with dermis infiltration and lymph node metastasis in EMPD. The expression of CD44v6 in EMPD closely relates to that of OPN,indicating that they may play a cooperative role in this process.