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切除的非小细胞肺癌中表皮生长因子受体(EGFR)突变与磷酸化EGFR表达

Epidermal growth factor receptor (EGFR) mutation and p-EGFR expression in resected non-small cell lung cancer.

作者信息

McMillen Elizabeth, Ye Fei, Li Guanghu, Wu Yong, Yin Guanghao, Liu Wei

机构信息

Department of Pathology, Mount Sinai School of Medicine, New York, New York, USA.

出版信息

Exp Lung Res. 2010 Nov;36(9):531-7. doi: 10.3109/01902148.2010.482176.

Abstract

Lung cancer, specifically non-small cell lung cancer (NSCLC), is a leading cause of mortality worldwide. In China, a dramatic increase in the incidence of NSCLC is expected in the next 20 years (Molina et al. Mayo Clin Proc. 2008;83:584–594). Mutated epidermal growth factor receptor (EGFR) status is a known predictor of response to tyrosine kinase inhibitors (TKIs), and immunohistochemistry may be a less costly way of predicting presence of mutation. In this study, mutation analysis of EGFR in 218 cases of NSCLC was performed. One hundred thirty tissue samples were examined via immunohistochemistry of p-EGFR (Y1045 and Y1068) and correlated with mutation status. Mutations were seen in 29% of patients, and were correlated with female sex, nonsmoking history, and adenocarcinoma histology. Phosphorylation at Y1045 was noted in 52% of cases, but in 71% of cases with EGFR mutation (P = .003). Phosphorylation of Y1068 was seen in 55% of cases but in 73% of cases with EGFR mutation (P = .006). This study correlating EGFR mutation with p-EGFR expression in resected NSCLC is one of the largest to date, although TKI response could not be assessed. The data show that, among Chinese patients, detection of p-1045 and p-1068 expression with immunohistochemistry predicts EGFR mutations. Immunohistochemical analysis of p-EGFR may be useful to predict responses to TKI therapy, although future studies are necessary.

摘要

肺癌,尤其是非小细胞肺癌(NSCLC),是全球主要的死亡原因之一。在中国,预计未来20年NSCLC的发病率将急剧上升(莫利纳等人,《梅奥临床学报》。2008年;83:584 - 594)。表皮生长因子受体(EGFR)突变状态是已知的酪氨酸激酶抑制剂(TKIs)反应预测指标,免疫组化可能是预测突变存在的成本较低的方法。在本研究中,对218例NSCLC患者进行了EGFR突变分析。通过p - EGFR(Y1045和Y1068)免疫组化检查了130份组织样本,并与突变状态相关联。29%的患者出现突变,且与女性、无吸烟史和腺癌组织学相关。52%的病例中观察到Y1045磷酸化,但在71%的EGFR突变病例中观察到(P = 0.003)。55%的病例中观察到Y1068磷酸化,但在73%的EGFR突变病例中观察到(P = 0.006)。尽管无法评估TKI反应,但本研究将切除的NSCLC中EGFR突变与p - EGFR表达相关联,是迄今为止规模最大的研究之一。数据表明,在中国患者中,通过免疫组化检测p - 1045和p - 1068表达可预测EGFR突变。p - EGFR的免疫组化分析可能有助于预测TKI治疗反应,尽管未来仍需开展研究。

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