Predictive Value of EGFR-PI3K-pAKT-mTOR-pS6 Pathway in Sinonasal Squamous Cell Carcinomas

Abstract

Background and objectivesWe have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical–pathological parameters and follow-up of sinonasal squamous cell carcinoma. Material and methodsThe immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC. ResultsLoss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (P=.005). Overexpression of pS6 was associated with a decrease in survival (P=.008), presence of local recurrences (P=.055), and worsening of overall prognosis (P=.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied. ConclusionsAlterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker.