Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib
Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib
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DOI：
10.1093/annonc/mdl077
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发表时间：
2006-07-01
影响因子：
50.5
通讯作者：
Hirsch, F. R.
中科院分区：
文献类型：
--
作者：
Cappuzzo, F.;Toschi, L.;Hirsch, F. R.
背景：本研究的目的是评估 PTEN 缺失和胰岛素样生长因子受体 1 (IGFR-1) 表达是否是酪氨酸激酶抑制剂 (TKI) 吉非替尼内在耐药的原因。患者和方法：通过免疫组织化学分析 124 名接受吉非替尼治疗的晚期非小细胞肺癌 (NSCLC) 患者的 PTEN 和 IGFR-1 表达。结果：IGFR-1 在77 例患者中，30 例（39.0%）结果呈阳性。 IGFR-1表达与临床或生物学特征没有显着相关性。 IGFR-1+ 和 IGFR-1- 之间对吉非替尼治疗的反应（16.7% 与 12.8%，P = 0.74）和进展时间（2.6 个月与 3.06 个月，P = 0.83）没有差异。 IGFR-1+ 患者的中位生存期显着更长（17.8 个月与 7.3 个月，P = 0.013）。成功评估了 93 例 PTEN 表达。在 19 个肿瘤（20.4%）中检测到 PTEN 缺失，且与任何临床或生物学特征无关。 PTEN+ 和 PTEN- 患者之间在反应、进展时间和生存方面没有观察到差异。在多变量分析中，IGFR-1 阴性状态与较高的死亡风险显着相关（风险比 2.21，P = 0.012）。结论：IGFR-1 表达和 PTEN 缺失与吉非替尼的内在耐药性无关。应进一步评估这两种生物标志物作为获得性耐药决定因素的临床相关性，以及未接触 TKI 的患者中 IGFR-1 表达的预后作用。
Background: The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib.Patients and methods: One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry.Results: IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological characteristic. No difference in terms of response, time to progression and survival was observed between PTEN+ and PTEN- patients. In multivariable analysis IGFR-1 negative status was significantly associated with higher risk of death (hazard ratio 2.21, P = 0.012).Conclusions: IGFR-1 expression and loss of PTEN are not associated with intrinsic resistance to gefitinib. Clinical relevance of these two biomarkers as determinant for acquired resistance, and the prognostic role of IGFR-1 expression in patients not exposed to TKIs should be evaluated further.