Division of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Br J Cancer. 2010 Jan 5;102(1):165-72. doi: 10.1038/sj.bjc.6605473. Epub 2009 Dec 8.
Evidence suggests that epidermal growth factor receptor (EGFR)-activation status may better predict the clinical behaviour of colon cancers than does EGFR expression. However, the prognostic effect of phospho-EGFR in primary colon cancer remains undefined.
Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n=388). Staining intensity was scored and correlated with clinicopathological variables, DNA mismatch repair (MMR) status, rates of cell proliferation (Ki-67), apoptosis (caspase-3), and patient survival.
Phospho-EGFR expression was detected in 157 of 388 (40%) tumours, whereas EGFR was found in 214 of 361 (59%). Although phospho-EGFR was unrelated to clinicopathological variables, strong EGFR intensity was associated with higher tumour stage (P=0.03). Tumours overexpressing EGFR (P=0.0002) or phospho-EGFR (P=0.015) showed increased Ki-67, but not caspase-3 expression. Phospho-EGFR was not prognostic. EGFR intensity was associated with worse disease-free survival (DFS) (hazard ratio (HR): 1.21 (1.03, 1.41); P=0.019) and overall survival (OS) (HR: 1.19 (1.02, 1.39); P=0.028). Tumours expressing both EGFR and phospho-EGFR had similar survival as EGFR alone. Stage and lymph node number were prognostic for DFS and OS, and histological grade for OS. EGFR was an independent predictor of DFS (P=0.042) after adjustment for stage, histological grade, age, and MMR status.
Phospho-EGFR and EGFR expression were associated with tumour cell hyperproliferation. Phospho-EGFR was not prognostic, whereas increased EGFR intensity was independently associated with poor DFS.
有证据表明，表皮生长因子受体（EGFR）的激活状态可能比 EGFR 表达更能预测结肠癌的临床行为。然而，磷酸化 EGFR 在原发性结肠癌中的预后作用仍未确定。
在完成辅助治疗试验的 TNM 分期 II 期和 III 期结肠癌的组织微阵列中，通过免疫组织化学（IHC）分析磷酸化 EGFR（Tyr-1173）和 EGFR 的表达。对染色强度进行评分，并与临床病理变量、DNA 错配修复（MMR）状态、细胞增殖（Ki-67）、凋亡（caspase-3）和患者生存相关。
在 388 例肿瘤中有 157 例（40%）检测到磷酸化 EGFR 表达，而在 361 例中有 214 例（59%）检测到 EGFR 表达。虽然磷酸化 EGFR 与临床病理变量无关，但强 EGFR 强度与更高的肿瘤分期相关（P=0.03）。过度表达 EGFR（P=0.0002）或磷酸化 EGFR（P=0.015）的肿瘤显示 Ki-67 表达增加，但 caspase-3 表达没有增加。磷酸化 EGFR 没有预后意义。EGFR 强度与无病生存期（DFS）（危险比（HR）：1.21（1.03，1.41）；P=0.019）和总生存期（OS）（HR：1.19（1.02，1.39）；P=0.028）相关。同时表达 EGFR 和磷酸化 EGFR 的肿瘤的生存情况与单独表达 EGFR 相似。分期和淋巴结数是 DFS 和 OS 的预后因素，组织学分级是 OS 的预后因素。在调整分期、组织学分级、年龄和 MMR 状态后，EGFR 是 DFS 的独立预测因素（P=0.042）。
磷酸化 EGFR 和 EGFR 表达与肿瘤细胞过度增殖有关。磷酸化 EGFR 没有预后意义，而 EGFR 强度增加与不良的 DFS 独立相关。
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