Expression of midkine in benign, premalignant and malignant vulvar tumors.

OBJECTIVE

To clarify the role of midkine (MK) in vulvar carcinogenesis though examination of its expression in vulvar lesions including vulvar condyloma acuminata (VCA), vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinomas (VSCC), and to analyze the relationship between MK expression and human papilloma virus (HPV) infection.

METHODS

Thirty VSCC, 15 VIN and 10 VCA patients were studied by streptavidin-biotin-immunoperoxidase method. MK expression was compared with clinicopathologic features of vulvar tumors.

RESULTS

MK was expressed in 26 of 30 VSCC (87%), 3 of 5 VIN III and all VCA samples, whereas no MK expression was detected in the VIN I-II samples or in normal epithelium. The difference of MK expression between VIN III and VSCC was statistically significant (P < 0.05). MK was more intensely expressed in differentiated-type (well differentiated and moderately differentiated) VSCC than in undifferentiated-type (poorly differentiated) VSCC. There was no statistically significant correlation between MK expression and clinical stage, lymph node metastasis and HPV infection in VSCC. MK expression were observed in all HPV-positive specimens including 2 VSCC, 1 VIN III and all VCA.

CONCLUSIONS

MK gene expression may be a late event in vulvar squamous cell malignant transformation, and may be associated with vulvar tumor cell differentiation. HPV-positive vulvar tumors expressed MK protein.