High expression of SALL4 is associated with poor prognosis in squamous cell carcinoma of the uterine cervix

Int J Clin Exp Pathol. 2018 Mar 1;11(3):1391-1398. eCollection 2018.

Abstract

Background: The zinc-finger transcription factor Sal-like protein 4 (SALL4) plays a pivotal role in tumor invasion and metastasis. Here, we investigated the clinicopathological significance of SALL4 overexpression in cervical squamous cell carcinoma (SCC) of the uterine cervix. Methods: SALL4 immunohistochemical staining was performed on cervical SCC specimens from 129 patients, as well as 98 cases of cervical squamous intraepithelial lesion (LSIL and HSIL) and 29 normal cervix samples. SALL4 immunofluorescence staining was performed in CaSki and SiHa cervical cancer cells. Statistical analyses were applied to evaluate correlations between SALL4 overexpression and clinicopathological features of SCC patients. Survival rates were calculated using the Kaplan-Meier method, and relationships between prognostic factors and patient survival were analyzed using Cox proportional hazard models. Results: SALL4 protein showed mainly nuclear staining in cervical cancer cells. Strong diffuse SALL4 staining was frequently seen in cervical cancer compared with normal tissues. SALL4 expression was significantly higher in cervical cancers than in LSIL, HSIL, and normal cervical epithelia. SALL4 overexpression was positively correlated with poor differentiation, late-stage, and lymph node metastasis. Moreover, the 5-year survival rate of early-stage cervical cancer patients with high SALL4 expression was significantly lower than patients with low SALL4 expression. Multivariate analysis suggested that SALL4 protein expression is an independent risk factor for survival in SCC. Conclusions: SALL4 plays an important role in SCC progression. High-level SALL4 expression is an independent prognostic factor of poor outcomes in SCC.

Keywords: SALL4; cervical cancer; immunohistochemistry; prognosis.