SOX2 expression in the pathogenesis of premalignant lesions of the uterine cervix: its histo-topographical distribution distinguishes between low- and high-grade CIN

Abstract

SOX2 expression in high-grade cervical intraepithelial neoplasia (CIN3) and cervical squamous cell carcinoma is increased compared to that in the normal cervical epithelium. However, data on the expression and histological distribution of SOX2 in squamous epithelium during progression of CIN are largely lacking. We studied SOX2 expression throughout the epithelium in 53 cases of CIN1, 2, and 3. In general, SOX2 expression increased and expanded from basal/parabasal to the intermediate/superficial compartment during early stages of progression of CIN. An unexpected, specific expression pattern was found in areas classified as CIN2 and CIN3. This pattern was characterized by the absence or low expression of SOX2 in the basal/parabasal compartment and variable levels in the intermediate and superficial compartments. It was significantly associated with CIN3 (p = 0.009), not found in CIN1 and only seen in part of the CIN2 lesions. When the different patterns were correlated with the genetic make-up and presence of HPV, the CIN3-related pattern contained HPV-positive cells in the basal/parabasal cell compartment that were disomic. This is in contrast to the areas exhibiting the CIN1 and CIN2 related patterns, which frequently exhibited aneusomic cells. Based on their SOX2 localisation pattern, CIN1 and CIN2 could be delineated from CIN3. These data shed new light on the pathogenesis and dynamics of progression in premalignant cervical lesions, as well as on the target cells in the epithelium for HPV infection.

In focus in HCB

“…Cytopathologic and histopathological observations can be correlated using the cervical intraepithelial neoplasia (CIN) three-tiered scale based upon the degree of lesion differentiation (Ismail et al 1989). Since expression of the transcription factor SOX2 is thought to increase during the progression from CIN to cervical cancer (Chang et al 2015;Moshi et al 2020), Moshi et al (2022) have now undertaken an investigation of the histotopographical distribution patterns of SOX2 immunostaining during the CIN1-3 stages, while correlating the staining patterns with Sox2 gene expression and human papilloma virus (HPV) load. In the normal cervix samples, they found that SOX2 immunostaining was expressed strongly in the squamous epithelial basal and parabasal layers, but was not detectable in the endocervical columnar and reserve cells.…”