Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer

The prognosis of patients with locally advanced cervical cancer (LACC) is often poor due to high treatment resistance. The present study aimed to investigate the association between the levels and localization of SET domain-containing protein 2 (SETD2) and glioma-associated oncogene homolog 1 (GLI1) proteins, which are implicated in CC, and their association with clinical outcomes in patients with LACC. In total, 84 patients with LACC diagnosed at Instituto Nacional de Cancerología (México City, México) between January 2016 and December 2018 were analyzed. Immunohistochemical staining was performed to evaluate the expression and localization of SETD2 and GLI1 proteins and immunoreactivity score (IS) was calculated. The association between IS and protein localization and clinicopathological factors and clinical outcomes was examined using the log-rank test and Cox regression model to investigate the disease-free survival (DFS) and overall survival (OS). The median age of the cohort was 46 years (range, 25-81 years). Analysis of SETD2 and IS values according to the sociodemographic and histopathological characteristics of the patients demonstrated that increased nuclear GLI1 (nGLI1) levels were significantly associated with a history of hormonal contraceptive use (P=0.029). Patients with nGLI1 IS >6 exhibited significantly worse OS (P=0.004) and DFS rates (P=0.013) compared with those with nGLI1 (IS <6). The univariate analysis revealed that lower OS was associated with nGLI IS >6 [hazard ratio (HR), 1.50; 95% CI, 1.44-14.13; P=0.010] and ncGLI1 IS <6 (HR, 1.86; 95% CI, 1.42-29.5; P=0.016), whereas a lower probability of DFS was significantly correlated with nGLI IS >6 (HR, 1.53; 95% CI, 1.23-17.49; P=0.023). The present study results demonstrated the utility of IS in evaluating the prognostic impact of SETD2 and GLI1 expression in patients with LACC.