PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients.
PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients.
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DOI：
10.1038/sj.bjc.6604009
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发表时间：
2007-10-22
影响因子：
8.8
通讯作者：
Mazzucchelli, L
中科院分区：
文献类型：
--
作者：
Frattini, M;Saletti, P;Romagnani, E;Martin, V;Molinari, F;Ghisletta, M;Camponovo, A;Etienne, L L;Cavalli, F;Mazzucchelli, L
评价表皮生长因子受体（EGFR）、K-Ras和PTEN（EGFR信号通路的所有成员）是否可能影响西妥昔单抗治疗的转移性结直肠癌（mCRC）患者的临床应答。评价了27例西妥昔单抗治疗的mCRC患者的药物反应，并研究了EGFR蛋白表达和基因状态、K-Ras突变状态和PTEN蛋白表达。10例患者对基于西妥昔单抗的治疗达到部分应答（PR）。所有27例患者均显示EGFR蛋白过表达。27例患者中有8例（30%）观察到表皮生长因子受体基因扩增，16例（59%）患者出现7号染色体标记的多体性。EGFR基因扩增组8例中6例部分缓解，多体性组16例中4例部分缓解，正常组3例无缓解（P<0.05）。K-Ras野生型17例，其中9例发生PR;突变型10例，其中1例发生PR（P<0.05）。16例患者的PTEN蛋白表达正常，其中10例达到PR，而11例PTEN活性丧失的患者则无明显获益（P<0.001）。EGFR基因扩增或7号染色体标记多体性的患者对西妥昔单抗有反应。除了K-Ras突变，我们首次证明了PTEN蛋白表达的缺失与对西妥昔单抗的无反应性有关。
To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients. Twenty-seven cetuximab-treated mCRC patients were evaluated for drug response and investigated for EGFR protein expression and gene status, K-Ras mutational status and PTEN protein expression. Ten patients achieved a partial response (PR) to cetuximab-based therapy. All 27 patients showed EGFR protein overexpression. Epidermal growth factor receptor gene amplification was observed in eight out of 27 (30%) and chromosome 7 marked polysomy in 16 (59%) patients. Partial response was observed in six out of eight patients with EGFR gene amplification, four out of 16 with marked polysomy and none out of three with eusomy (P<0.05). The K-Ras wild-type sequence was observed in 17 patients, and nine of them experienced a PR. Conversely, K-Ras was mutated in 10 cases, of which one patient experienced a PR (P<0.05). The PTEN protein was normally expressed in 16 patients, and 10 of them achieved a PR. In contrast, no benefit was documented in 11 patients with loss of PTEN activity (P<0.001). Patients with EGFR gene amplification or chromosome 7 marked polysomy respond to cetuximab. In addition to K-Ras mutations, we demonstrate for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab.