Expression of CK17 and SOX2 in Vulvar Intraepithelial Neoplasia: A Comprehensive Analysis of 150 Vulvar Lesions

Recently, the immunohistochemical markers cytokeratin 17 (CK17) and SRY-box2 (SOX2) have been evaluated as adjuncts for the diagnosis of high-grade vulvar intraepithelial neoplasia (VIN). In the present study, the aim was to assess CK17 and SOX2 expression in VIN by studying 150 vulvar lesions, originally reported as high-grade VIN and to assess the diagnostic accuracy.

All slides (H&E, p16^INK4a, p53, Ki-67, CK17, and SOX2 stains) were independently assessed by six pathologists and the final diagnosis was reached in consensus meetings, as follows: 46 human papillomavirus (HPV)-independent VIN (including 30 p53 mutant and 16 p53 wild-type lesions), 58 high-grade squamous intraepithelial lesions (HSILs), 4 low-grade SILs (LSILs), 37 non-dysplastic lesions, and 5 lesions where the histology was inconclusive.

CK17 positivity was observed in 100% p53 wild-type HPV-independent VIN, compared to 73% p53 mutant HPV-independent VIN, 14% HSILs, 0% LSILs, and 24% non-dysplastic lesions. SOX2 positivity was observed in 13% p53 wild-type HPV-independent VIN, 43% p53 mutant HPV-independent VIN, 2% HSILs, 0% LSILs, and 3% non-dysplastic lesions. The highest diagnostic accuracy (89%) for HPV-independent VIN was obtained when combining p53 and CK17 immunohistochemistry. The addition of SOX2 did not further increase diagnostic accuracy.

To conclude, aside from p53, both CK17 and SOX2 can be of value for reaching an accurate diagnosis of HPV-independent VIN.