Expression of the stem cell markers NANOG and SOX2 in the cervical squamous carcinogenesis.

Abstract

Background. The aim of the present study was to assess a diagnostic potential of cancer stem cell (CSC) markers NANOG and SOX2 for classifying cervical squamous intraepithelial lesions (SILs)/cervical intraepithelial neoplasia (CIN).

Patients and methods. NANOG and SOX2 expression was evaluated immunohistochemically on 40 patients: in 10 cases each of low-grade SIL (LSIL), high-grade SIL/CIN, grade 2 (HSIL/CIN 2), HSIL/CIN grade 3 (HSIL/CIN 3), cervical squamous cell carcinoma (CSCC) and their adjacent non-dysplastic squamous epithelium. In addition, HPV genotyping and immunohistochemical staining with p16 and Ki-67 were done. NANOG and SOX2 expression was compared between squamous lesions and controls and between squamous lesions by multiplying staining intensity (SI) by the percentage of positive cells (P) and by multiplying SI by the thickness of staining in epithelium (T) to calculate SIxP and SIxT score.

Results. NANOG and SOX2 expression gradually increased from controls via LSIL and HSIL to CSCC. LSIL showed higher NANOG and SOX2 expression than controls (P<0.05 for NANOG SIxP and SIxT scores and SOX2 SIxT score) and lower NANOG and SOX2 expression than HSIL (P<0.05 for all SIxP and SIxT scores). HSIL/CIN 3 showed higher SOX2 expression than HSIL/CIN 2 (P<0.05 for SIxP and SIxT scores).

Conclusions. NANOG and SOX2 expression is higher in SILs and CSCC than in non-dysplastic squamous epithelium. In contrast to p16, NANOG and SOX2 could be effective for distinguishing LSIL from cervical non-dysplastic squamous epithelium. NANOG and SOX2 could be surrogate markers for differentiating LSIL from HSIL. Moreover, SOX2 could be helpful for distinguishing HSIL/CIN 2 from HSIL/CIN 3.