Abstract
The prognosis of pharyngeal carcinoma is poorest of all head and neck cancers and the survival rate has not improved in the last two decades. Epithelial-mesenchymal transition (EMT) is a complex process during which epithelial cells lose their arrangement and attain motile and migratory characteristics. It is a crucial process in tumorigenesis enabling tumor cells to invade and metastasize. Transcription factor SIP1 is a key regulator of EMT. The objective of this study was to evaluate the significance of SIP1 in pharyngeal squamous cell carcinoma (PSCC) progression and prognosis. Our material consists of clinicopathological information, follow-up data and tissue samples of 109 patients diagnosed with PSCC. Immunohistochemistry was used to evaluate the expression of SIP1 in tumor epithelial cell, stromal cell and endothelial cell nuclei. Tumors with positive epithelial SIP1 immunostaining were more advanced (SIII-IV, p = 0.02) and had more lymph node metastases ( p = 0.04). There were also more often second primaries diagnosed in that group ( p = 0.048). Tumors with positive stromal staining of SIP1 relapsed more often than SIP1 negative tumors ( p = 0.007). Patients with Sip1 epithelial or stromal immunopositive tumors had significantly lower 5-year disease specific and overall survival than patients with SIP1 negative tumors ( p = 0.012 and p = 0.003 for epithelial reactivity, p = 0.018 and p = 0.003 for stromal reactivity respectively). Also in Cox proportional hazards model SIP1 epithelial immunoreactivity was an independent prognostic factor for disease specific survival ( p = 0.045) together with Karnofsky performance status score and T-class ( p < 0.001 in both). SIP1 expression in tumor epithelial or stromal nuclei is related to cancer progression and is an important prognostic factor in PSCC. Sip1 may have a role as a new biomarker indicating aggressive tumors with poor prognosis.
Published Version
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