Massarelli Erminia, Liu Diane D, Lee J Jack, El-Naggar Adel K, Lo Muzio Lorenzo, Staibano Stefania, De Placido Sabino, Myers Jeffrey N, Papadimitrakopoulou Vassiliki A
Department of Head & Neck/Thoracic Medical Oncology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2005 Dec 1;104(11):2430-6. doi: 10.1002/cncr.21476.
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.
近期数据显示,磷酸化Akt(p-Akt)与头颈部鳞状细胞癌(HNSCC)放疗后局部疾病控制失败之间存在显著关联,且Akt激活与HNSCC从癌前病变发展为浸润性癌的组织学进展相关。本研究评估了Akt在口腔先前未治疗的癌前病变和浸润性舌癌中对患者预后及癌症发展的作用。
使用磷酸化状态特异性抗体(Ser 473)通过免疫组织化学法评估舌癌和口腔癌前病变标本中蛋白激酶B/Akt(PKB/Akt)的激活情况。
在52例可获得的舌癌病例中,24例(46%)检测到p-Akt表达;在22例可获得的癌前病变中,10例(45%)检测到p-Akt表达。在舌癌中,中位随访时间为7.3年,复发(17例中的15例,88%)或死于癌症(12例中的10例,83%)的病例中p-Akt高表达。无论分期和淋巴结状态如何,Akt表达阳性的病例无病生存期显著缩短(对数秩检验,P < 0.0001)。
p-Akt表达与舌癌患者较差的预后相关。这一发现凸显了Akt作为预后标志物和分子治疗潜在靶点的潜在作用。