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澳门非小细胞肺癌中驱动基因突变、其相关蛋白表达与生存之间的关系

Relationship between driver gene mutations, their relative protein expressions and survival in non-small cell lung carcinoma in Macao.

作者信息

Chan Kin Iong, Vong Hong Ting, Sin Lai Fong, Yip Yuk Ching, Zhong Xue Yun, Wen Jian Ming

机构信息

Department of Pathology, Kiang Wu Hospital, Macau Special Administrative Region, Macau, China.

Department of Pathology, Medical School, Jinan University, Guangzhou 510632, China.

出版信息

Clin Respir J. 2018 Apr;12(4):1416-1423. doi: 10.1111/crj.12670. Epub 2017 Aug 9.

Abstract

OBJECTIVES

We report the status of most common gene mutations in non-small cell lung carcinoma (NSCLC) in Macao, and explore the relationship between each gene mutation and clinicopathologic features and survival.

METHODS

EGFR, KRAS and BRAF mutations were detected by PCR in 122 cases of NSCLC. ALK translocation and MET amplification were detected by fluorescence in situ hybridization (FISH). MET and thyroid transcription factor (TTF-1) were investigated by immunohistochemistry. Clinical data were collected for analyzing their correlation with the gene mutations.

RESULTS

The mutation of EGFR, KRAS and BRAF was detected in 48 (39.3%), 13 (10.7%) and 3 (2.5%) of 122 cases of NSCLC, respectively. ALK translocation and MET amplification were detected in 7 (5.7%) and 3 cases (2.5%). The rate of EGFR mutation was significantly higher in female and non-smoker patients. In TTF-1 positive cases EGFR mutation was more frequent. Age of the patients over 62-year old was correlated with KRAS mutations. The concordance between ALK IHC and FISH was 58.3%. The MET protein in the cases with MET amplification was 100% positive. The survival was lower in the patients with positive MET protein than those with negative. MET protein was an independent prognostic factor for NSCLC.

CONCLUSIONS

EGFR mutation occurred frequently in the female never smoke patients with NSCLC. KRAS mutation was more common in old patients. Negative MET protein expression could be used as a negative predictive marker of MET amplification. MET protein expression was an independent prognostic factor for NSCLC.

摘要

目的

我们报告了澳门非小细胞肺癌(NSCLC)中最常见基因突变的情况,并探讨了每种基因突变与临床病理特征及生存之间的关系。

方法

采用聚合酶链反应(PCR)检测122例NSCLC患者的表皮生长因子受体(EGFR)、 Kirsten大鼠肉瘤病毒癌基因(KRAS)和B-Raf原癌基因(BRAF)突变。采用荧光原位杂交(FISH)检测间变性淋巴瘤激酶(ALK)易位和间质表皮转化因子(MET)扩增。通过免疫组织化学检测MET和甲状腺转录因子(TTF-1)。收集临床数据以分析其与基因突变的相关性。

结果

122例NSCLC患者中,EGFR、KRAS和BRAF突变分别在48例(39.3%)、13例(10.7%)和3例(2.5%)中被检测到。ALK易位和MET扩增分别在7例(5.7%)和3例(2.5%)中被检测到。女性和非吸烟患者的EGFR突变率显著更高。在TTF-1阳性病例中,EGFR突变更常见。62岁以上患者的年龄与KRAS突变相关。ALK免疫组织化学与FISH之间的一致性为58.3%。MET扩增病例中的MET蛋白100%呈阳性。MET蛋白阳性患者的生存率低于阴性患者。MET蛋白是NSCLC的独立预后因素。

结论

EGFR突变在女性非吸烟NSCLC患者中频繁发生。KRAS突变在老年患者中更常见。MET蛋白阴性表达可作为MET扩增的阴性预测标志物。MET蛋白表达是NSCLC的独立预后因素。

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