SIP1 predicts progression and poor prognosis in pharyngeal squamous cell carcinoma

Abstract

Objectives: The epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis that enables tumor cells to invade and metastasize. The transcription factors SIP1, SLUG, ZEB1, SNAI1, and TWIST are fundamental in regulating EMT. We investigated the relationships between several clinicopathological variables, prognosis, and SIP1, SLUG, or ZEB1 in a retrospective pharyngeal squamous cell carcinoma (PSCC) cohort. Study Design: Immunohistochemistry was used to evaluate the expression of SIP1, SLUG, and ZEB1 in 108 tumor samples from a retrospective cohort of patients with PSCC. Results: Tumors with positive epithelial SIP1 immunostaining were more advanced (SIII-IV, p=0.02) and had more lymph node metastases (p=0.04) than SIP1-negative tumors. Tumors with positive stromal staining of SIP1 relapsed more often than SIP1-negative tumors (p=0.007). Negative SIP1 immunoreactivity correlated significantly with better disease-specific survival (DSS) and better overall survival (OS) (p=0.012 and p=0.003 for epithelial reactivity, p=0.018 and p=0.003 for stromal reactivity, respectively). Lack of epithelial SIP1 expression remained an independent and favorable prognostic factor in a Cox proportional hazards model (p=0.046), together with high Karnofsky performance status score and low T class (p<0.001 for both). Co-expression of SNAI1, TWIST, and SIP1 in tumor epithelium predicted even shorter DSS than SIP1 expression alone (p<0.001) in the present study cohort. Conclusions: SIP1 is related to cancer progression and appears to be an independent prognostic factor in PSCC.