Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status.
Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status.
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DOI：
10.1038/sj.bjc.6605473
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发表时间：
2010-01-05
影响因子：
8.8
通讯作者：
Sinicrope, F. A.
中科院分区：
文献类型：
--
作者：
Rego, R. L.;Foster, N. R.;Smyrk, T. C.;Le, M.;O'Connell, M. J.;Sargent, D. J.;Windschitl, H.;Sinicrope, F. A.
有证据表明，表皮生长因子受体(EGFR)的激活状态可能比EGFR的表达更好地预测结肠癌的临床行为。然而，磷酸化的EGFR在原发性结肠癌中的预后作用仍不明确。采用免疫组织化学方法(IHC)检测388例已完成的TNM II、III期结肠癌组织芯片中磷酸化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、细胞增殖率(Ki-67)、细胞凋亡率(caspase-3)和患者生存相关。388个肿瘤中有157个(40%)表达磷酸化EGFR，而361个肿瘤中有214个(59%)有EGFR表达。虽然磷酸化的EGFR与临床病理变量无关，但较强的EGFR强度与较高的肿瘤分期有关(P=0.03)。过度表达表皮生长因子受体(P=0.0002)或磷酸化表皮生长因子受体(P=0.015)的肿瘤，Ki-67表达增加，而caspase-3表达不明显。磷酸化EGFR不能预测预后。无病生存率(HR)和总生存率(OS)分别为危险比(HR)1.21(1.03，1.41；P=0.019)和总生存率(HR：1.19(1.02，1.39)；P=0.028)。同时表达EGFR和磷酸化EGFR的肿瘤与单独表达EGFR的肿瘤存活率相似。分期和淋巴结数目是DFS和OS的预后因素，组织学分级是OS的预后因素。在调整了分期、组织学分级、年龄和MMR状态后，表皮生长因子受体是DFS的独立预测因子(P=0.042)。磷酸化EGFR和EGFR的表达与肿瘤细胞的过度增殖有关。磷酸化的EGFR不能预测预后，而EGFR强度升高与DFS差独立相关。
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.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
45.3
作者：
Cesana, GC;DeRaffele, G;Kaufman, HL
通讯作者：
Kaufman, HL
影响因子：
45.3
作者：
Garrity, MM;Burgart, LJ;Witzig, TE
通讯作者：
Witzig, TE
影响因子：
8.4
作者：
McKay, JA;Murray, LJ;McLeod, HL
通讯作者：
McLeod, HL
影响因子：
4.8
作者：
Chattopadhyay, A;Vecchi, M;Carpenter, G
通讯作者：
Carpenter, G