GLUT1 Expression Patterns in Verruciform Acanthotic Vulvar Squamous Intraepithelial Neoplasia, HPV-Independent p53...

Verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN) is a rare type of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (SCC) precursor lacking aberrant p53 expression. Our recent study demonstrated GLUT1 overexpression in vulvar SCC and identified 2 distinct patterns in HPV-associated high-grade squamous intraepithelial lesions and HPV-independent differentiated vulvar intraepithelial neoplasia. Herein, we expand on our study by assessing GLUT1 expression in 24 cases of vaVIN and 8 cases of associated invasive SCC, compared with 48 cases of benign vulvar squamous lesions, including 40 cases of non-HPV benign vulvar lesions and 8 cases of condyloma associated with low-risk HPV infection. GLUT1 immunohistochemistry (IHC) demonstrated consistent diffuse GLUT1 immunostaining in all vaVIN cases. The GLUT1 immunostaining pattern in vaVIN is characterized by strong membranous staining in the basal layer with suprabasal extension to the full thickness of intermediate layers. In vulvar SCC associated with vaVIN, GLUT1 expression was prominent at the periphery of tumor nests without expression in the central portion. GLUT1 IHC revealed weak peri-papillae or intensified peri-papillae patterns in non-neoplastic vulvar lesions and HPV-related patterns in condyloma. The GLUT1 immunostaining patterns in vaVIN and associated SCC are different from benign mimickers, but similar to those of differentiated vulvar intraepithelial neoplasia and associated SCC, despite distinct molecular alterations and pathways. The latter suggests that upregulation of GLUT1 is likely a common metabolic pathway shared by 2 types of HPV-independent VINs, regardless of p53 status. GLUT1 IHC is highly sensitive in detecting vaVIN. However, the specificity rests on recognizing GLUT1-staining patterns in benign mimickers of vaVIN. Along with HPV chromogenic in situ hybridization and other well-characterized biomarkers, GLUT1 immunochemistry can be a helpful adjunct in assisting the diagnosis of vaVIN.