表皮生长因子受体（EGFR）和蛋白激酶 B1（AKT1）过表达相互排斥，与胃腺癌切除术后不良生存相关。
EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas.
机构信息
Medical Oncology, University Hospital of Pisa, 56126 Pisa, Italy.
Surgical Pathology, Unit 3, University Hospital of Pisa, 56126 Pisa, Italy.
出版信息
Cancer Biomark. 2018 Feb 14;21(3):731-741. doi: 10.3233/CBM-170865.
PURPOSE
The evaluation of molecular targets in gastric cancer has demonstrated the predictive role of HER2 amplification for trastuzumab treatment in metastatic gastric cancer. Besides HER2, other molecular targets are under evaluation in metastatic gastric tumors. However, very little is known about their role in resected tumors. We evaluated the expression of HER2, EGFR, MET, AKT1 and phospho-mTOR in resected stage II-III adenocarcinomas.
METHODS
Ninety-two patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated. Antibodies anti-HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded slides. Using FISH, HER2 amplification was evaluated in cases with an intermediate (+2) staining.
RESULTS
EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p= 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p= 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was not a prognostic factor by itself (p= 0.234). AKT1 and EGFR overexpression was mutually exclusive and patients with EGFR or AKT1 overexpression experienced a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p= 0.005).
CONCLUSIONS
EGFR is confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers.
目的
胃癌中分子靶点的评估显示 HER2 扩增可预测转移性胃癌曲妥珠单抗治疗的疗效。除 HER2 外，其他分子靶点也在转移性胃肿瘤中进行评估。然而，对于这些靶点在切除肿瘤中的作用，我们知之甚少。我们评估了 HER2、EGFR、MET、AKT1 和磷酸化-mTOR 在切除的 II-III 期腺癌中的表达。
方法
评估了 92 例接受胃（63%）或胃食管腺癌（27%）切除的患者。使用抗 HER2、EGFR、MET、AKT1 和磷酸化-mTOR 抗体对福尔马林固定石蜡包埋切片进行免疫染色。对于中间（+2）染色的病例，使用 FISH 评估 HER2 扩增。
结果
EGFR 过表达（11%）是总生存（3 年 OS：47%对 77%；Log-Rank p=0.033）的不良预后因素。MET 过表达（36%）与生存不良趋势相关（3 年 OS：65%对 77%；Log-Rank p=0.084）。HER2 扩增/过表达和 mTOR 过度磷酸化分别在 13%和 48%的肿瘤中观察到。AKT1 过表达（8%）本身不是预后因素（p=0.234）。AKT1 和 EGFR 过表达是相互排斥的，EGFR 或 AKT1 过表达的患者预后不良（3 年 OS：52%对 79%，Log-Rank p=0.005）。
结论
EGFR 被确认为切除的胃癌中的不良预后因素。我们首次描述了 EGFR 和 AKT1 的相互排斥过表达，具有潜在的预后意义，表明该途径与胃癌的生长有关。
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