Distinct Patterns of GLUT1 Expression in Human Papillomavirus Associated and Human Papillomavirus Independent Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma

Abstract

The expression of GLUT1 in vulvar squamous cell carcinoma (SCC) and its precursors remains largely unknown. We systematically investigated GLUT1 expression in human papillomavirus (HPV)–associated and HPV-independent vulvar intraepithelial neoplasia (VIN) and SCC. Our study had a total of 240 cases, including 40 cases of non-neoplastic vulva, 45 HPV-associated high-grade squamous intraepithelial lesions (HSILs), 65 HPV-independent VINs, and 90 invasive SCCs. Immunohistochemical analysis revealed that GLUT1 was expressed noncontinuously at the basal layer near stromal papillae in most non-neoplastic vulvar squamous epithelium. Overexpression of GLUT1 was observed in 82.2% and 88.9% of HPV-associated HSIL and SCC, respectively, compared with 96.9% and 100% of HPV-independent VIN and SCC. Two distinct patterns of the GLUT1 expression were observed in HPV-associated and HPV-independent VIN and SCC. In HPV-associated HSIL, overexpression of GLUT1 was mainly noted in the upper intermediate layers, accompanied by negative or weak immunostaining in the basal and parabasal layers. Similar patterns were also found in HPV-associated SCC, characterized by increased GLUT1 staining intensity in the centers of tumor sheets or nests with spared basal peripheral layers. Conversely, intense membranous GLUT1 staining was mainly observed in the basal and suprabasal layers in HPV-independent VIN, regardless of p53 status. Similar intense basal and parabasal GLUT1 staining patterns and no or weak staining intensity in central areas were seen in HPV-independent SCCs. In conclusion, overexpression of GLUT1 was found in most vulvar SCCs and their precursors. We identified 2 distinct GLUT1 patterns between HPV-associated and HPV-independent VINs and SCCs. Given its high sensitivity, immunohistochemistry for GLUT1 can be a valuable tool for facilitating accurate diagnosis of VIN, especially the HPV-independent type.