Akt activation correlates with adverse outcome in tongue cancer

Abstract

Recent data have shown a significant association between phosphorylated-Akt (p-Akt) and failure of local disease control by radiation therapy in head and neck squamous carcinoma (HNSCC), and also that Akt activation correlates with histologic progression of HNSCC from premalignant lesions to invasive cancer. This study evaluated the role of Akt in previously untreated preneoplastic lesions of oral cavity and invasive tongue carcinoma on patient outcome and cancer development. PKB/Akt activation was assessed by immunohistochemistry using a phosphorylation state-specific antibody (Ser 473) in tongue cancer and preneoplastic specimens of oral cavity. The expression of p-Akt was detected in 24 (46%) of the 52 available tongue cancer cases and in 10 (45%) of the 22 available preneoplastic lesions. In tongue cancer, with a median follow-up of 7.3 years, p-Akt was highly expressed in the cases that relapsed (15 of 17, 88%) or died of cancer (10 of 12, 83%). Disease-free survival was significantly shorter in cases with Akt expression (log rank test, P < 0.0001) independently of the stage and nodal status. Expression of p-Akt correlated with worse outcome in patients with tongue cancer. This finding highlights the potential role of Akt as a prognostic marker and as a potential target for molecular therapeutics.