Zhang Gloria, Yang Bin
Department of Pathology, Diagnostic Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.
Department of Pathology, Diagnostic Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.
Mod Pathol. 2025 Jul 3;38(11):100836. doi: 10.1016/j.modpat.2025.100836.
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.
葡萄糖转运蛋白1（GLUT1）在外阴鳞状细胞癌（SCC）及其癌前病变中的表达情况仍大多未知。我们系统地研究了GLUT1在人乳头瘤病毒（HPV）相关和HPV非相关的外阴上皮内瘤变（VIN）及SCC中的表达。我们的研究共纳入240例病例，包括40例非肿瘤性外阴、45例HPV相关的高级别鳞状上皮内病变（HSIL）、65例HPV非相关的VIN以及90例浸润性SCC。免疫组化分析显示，在大多数非肿瘤性外阴鳞状上皮中，GLUT1在靠近基质乳头的基底层呈间断性表达。与HPV非相关的VIN和SCC分别有96.9%和100%相比，HPV相关的HSIL和SCC中GLUT1过表达分别为82.2%和88.9%。在HPV相关和HPV非相关的VIN及SCC中观察到两种不同的GLUT1表达模式。在HPV相关的HSIL中，GLUT1过表达主要见于中上层，基底层和副基底层免疫染色阴性或弱阳性。HPV相关的SCC中也发现类似模式，其特征为肿瘤片层或巢中心的GLUT1染色强度增加，基底层周边 spared。相反，无论p53状态如何，HPV非相关的VIN中主要在基底层和基上层观察到强烈的膜性GLUT1染色。HPV非相关的SCC中也可见类似的强烈基底层和副基底层GLUT1染色模式，中心区域无染色或染色强度较弱。总之，大多数外阴SCC及其癌前病变中发现有GLUT1过表达。我们在HPV相关和HPV非相关的VIN及SCC之间鉴定出两种不同的GLUT1模式。鉴于其高敏感性，GLUT1免疫组化可为准确诊断VIN，尤其是HPV非相关类型提供有价值的工具。
