Downregulated CD44 and hyaluronan expression in vulvar intraepithelial neoplasia and squamous cell carcinomas.

OBJECTIVE

To investigate the expression of CD44 and hyaluronan in vulvar squamous cell carcinomas, vulvar intraepithelial neoplasia (VIN) and lichen sclerosus (LS) cases.

DESIGN

Retrospective study.

SETTING

Kuopio University Hospital in Finland.

SAMPLES AND

METHODS

A total of 18 vulvar squamous cell carcinomas, 22 VIN and 14 LS cases were studied by immunohistochemistry and histochemistry. Co-localization of these markers was also studied by dual fluorescence staining.

MAIN OUTCOME MEASURES: Expression and cellular localization of CD44 and hyaluronan. RESULTS. In the normal squamous cell epithelium and in most LS samples, CD44 and hyaluronan were expressed homogeneously along plasma membranes with extensive co-localization. In carcinomas and VIN, both CD44 and hyaluronan were mostly irregular and without co-localization. In most VIN samples, CD44 was membranous, while hyaluronan was intracellular in 45% of the cases. CD44 showed both plasma membrane and intracellular localization in 39% of the carcinomas and in 94% of the cases hyaluronan was located only intracellularly. In LS, stromal hyaluronan staining was stronger than in carcinomas (p = 0.01). CD44 and hyaluronan staining was not associated with the grade of VIN, while there was good differentiation in carcinomas associated with preserved membranous CD44 (p = 0.012). Hyaluronan was not associated with the grade or stage of cancer.

CONCLUSIONS

Differences in hyaluronan and CD44 expression in VIN and squamous cell carcinomas compared to normal epithelium suggest that they have a role in vulvar malignancy.