Analysis of SOX2 and SOX17 expression in cervical HPV-associated adenocarcinoma in situ: Correlation with histologic variants.

HPV-associated adenocarcinoma in situ (AIS) is the main precursor to endocervical adenocarcinoma. The differential immunoprofiles remain poorly characterized among HPV-associated AIS variants (such as usual-type and stratified mucin-producing intraepithelial lesion [SMILE]). This study aimed to investigate the expression of stem cell markers (SOX2 and SOX17) in 159 HPV-associated AIS (124 usual-type, 11 with intestinal differentiation, 24 SMILE) by immunohistochemistry. Compared to normal endocervical glands, AIS exhibited significantly increased expression of SOX2 (69.2% vs. 0, p < 0.001), but decreased SOX17 (40.9% vs. 98.1%, p < 0.001). Positive SOX2 and negative SOX17 had a specificity of 100% and 98.1% in the differential diagnosis of AIS from normal glands, respectively. SOX2 expression was significantly higher in SMILE (22/24, 91.7%) than in usual-type AIS (80/124, 64.5%, p = 0.030). In contrast, SOX17 expression was absent in all SMILE (0/24) and most AIS with intestinal differentiation (1/11, 9.1%), but was significantly higher in usual-type AIS (64/124, 51.6%, p < 0.001). The SOX2/SOX17 composite profile may aid in the diagnosis of AIS and its variants. The SOX2-positive (overexpression) /SOX17-negative profile suggest a divergent pathway with squamous differentiation potential in SMILE. These findings provide novel insights into the cellular histogenesis of AIS variants.