Akt activation correlates with adverse outcome in tongue cancer

Akt activation correlates with adverse outcome in tongue cancer
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DOI：
10.1002/cncr.21476
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发表时间：
2005-12-01
期刊：
CANCER
影响因子：
6.2
通讯作者：
Papadimitrakopoulou, VA
Papadimitrakopoulou, VA
中科院分区：
医学1区
文献类型：
--
作者：
Massarelli, E;Liu, DD;Papadimitrakopoulou, VA

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背景。最近的数据显示，磷酸化Akt （p-Akt）与头颈部鳞状癌（HNSCC）放射治疗局部疾病控制失败之间存在显著关联，Akt活化与HNSCC从癌前病变到浸润性癌的组织学进展相关。本研究评估了Akt在未经治疗的口腔和浸润性舌癌肿瘤前病变中对患者预后和癌症发展的作用。使用磷酸化状态特异性抗体（Ser 473）免疫组织化学方法评估舌癌和癌前口腔标本中PKB/Akt的活化情况。52例舌癌患者中有24例（46%）检测到p-Akt表达，22例癌前病变中有10例（45%）检测到p-Akt表达。在舌癌中，中位随访7.3年，p-Akt在复发（15 / 17,88%）或死于癌症（10 / 12,83%）的病例中高度表达。与分期和淋巴结状态无关，Akt表达的患者无病生存期显著缩短（log rank检验，P < 0.0001）。舌癌患者p-Akt表达与预后差相关。这一发现突出了Akt作为预后标记物和分子治疗的潜在靶点的潜在作用。
BACKGROUND. 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.METHODS. PKB/Akt activation was assessed by immunohistochemistry using a phosphorylation state-specific antibody (Ser 473) in tongue cancer and preneoplastic specimens of oral cavity.RESULTS. 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.CONCLUSIONS. 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.