Transforming growth factor beta1 (TGFbeta1) expression in head and neck squamous cell carcinoma patients as related to prognosis

Abstract

Background: Transforming growth factor beta1 (TGFbeta1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGFbeta1 responsiveness is a critical step in epithelial carcinogenesis.

Objective: To investigate the prognostic relevance of TGFbeta1 expression in head and neck squamous cell carcinoma (HNSCC).

Materials and methods: TGFbeta1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGFbeta-type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells.

Results: TGFbeta1-positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGFbeta1-positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P </= 0.001). TGFbeta1 was also not related to 5 years survival (Kaplan-Meier). Strong and diffuse expression of TGFbeta-RII was identified in 19/20 cases regardless of TGFbeta1 immunoreactivity. Out of 17 TGFbeta1-positive oral cavity/oropharynx tumors, only nine expressed TGFbeta-RI suggesting a disruption of the TGFbeta1 pathway. We conclude that TGFbeta1 protein immunostaining is not a useful biomarker in assessment of prognosis in HNSCC.