Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands.
Radiother Oncol. 2011 Oct;101(1):165-70. doi: 10.1016/j.radonc.2011.06.022. Epub 2011 Jul 19.
Overexpression of EGFR correlates with decreased survival after radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the contribution of the activated form, pEGFR, and its downstream signaling (PI3-K/AKT) pathway is not clear yet.
Fifty-eight patients with HNSCC were included in the study. pEGFR, pAKT, hypoxia, and vessels were visualized using immunohistochemistry. Fractions (defined as the tumor area positive for the respective markers relative to the total tumor area) were calculated by automated image analysis and related to clinical outcome.
Both pEGFR (median 0.6%, range 0-34%) and pAKT (median 1.8%, range 0-16%) expression differed between tumors. Also, a large variation in hypoxia was found (median pimonidazole fraction 3.9% 0-20%). A significant correlation between pEGFR and pAKT (r(s) 0.44, p=0.004) was seen, however, analysis revealed that this was not always based on spatial coexpression. Low pAKT expression was associated with increased risk of regional recurrence (p<0.05, log-rank) and distant metastasis (p=0.04).
The correlation between expression of pEGFR and pAKT is indicative of activation of the PI3-K/AKT pathway through phosphorylation of EGFR. Since not all tumors show coexpression to the same extent, other factors must be involved in the activation of this pathway as well.
表皮生长因子受体（EGFR）的过表达与头颈部鳞状细胞癌（HNSCC）患者放疗后生存率降低相关。然而，激活型 EGFR（pEGFR）及其下游信号通路（PI3-K/AKT）的作用尚不清楚。
本研究纳入 58 例 HNSCC 患者。采用免疫组化法检测 pEGFR、pAKT、缺氧和血管。通过自动图像分析计算各标志物的阳性肿瘤面积占比（定义为分数），并与临床结局相关联。
pEGFR（中位数 0.6%，范围 0-34%）和 pAKT（中位数 1.8%，范围 0-16%）的表达在肿瘤间存在差异。同时，缺氧的变异性较大（中位数 pimonidazole 分数为 3.9%，范围 0-20%）。pEGFR 与 pAKT 之间存在显著相关性（r(s) 0.44，p=0.004），然而分析表明这并不总是基于空间共表达。pAKT 表达水平较低与区域复发风险增加（p<0.05，log-rank）和远处转移（p=0.04）相关。
pEGFR 和 pAKT 的表达相关提示 EGFR 通过磷酸化激活了 PI3-K/AKT 通路。由于并非所有肿瘤都表现出相同程度的共表达，因此其他因素也可能参与了该通路的激活。
