Dataset Information

A large-scale cross-sectional study of ALK rearrangements and EGFR mutations in non-small-cell lung cancer in Chinese Han population.

ABSTRACT: The predictive power of age at diagnosis and smoking history for ALK rearrangements and EGFR mutations in non-small-cell lung cancer (NSCLC) remains not fully understood. In this cross-sectional study, 1160 NSCLC patients were prospectively enrolled and genotyped for EML4-ALK rearrangements and EGFR mutations. Multivariate logistic regression analysis was performed to explore the association between clinicopathological features and these two genetic aberrations. Receiver operating characteristic (ROC) curves methodology was applied to evaluate the predictive value. We showed that younger age at diagnosis was the only independent variable associated with EML4-ALK rearrangements (odds ratio (OR) per 5 years' increment, 0.68; p < 0.001), while lower tobacco exposure (OR per 5 pack-years' increment, 0.88; p < 0.001), adenocarcinoma (OR, 6.61; p < 0.001), and moderate to high differentiation (OR, 2.05; p < 0.001) were independently associated with EGFR mutations. Age at diagnosis was a very strong predictor of ALK rearrangements but poorly predicted EGFR mutations, while smoking pack-years may predict the presence of EGFR mutations and ALK rearrangements but with rather limited power. These findings should assist clinicians in assessing the likelihood of EML4-ALK rearrangements and EGFR mutations and understanding their biological implications in NSCLC.

SUBMITTER: Hong S

PROVIDER: S-EPMC4248273 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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A large-scale cross-sectional study of ALK rearrangements and EGFR mutations in non-small-cell lung cancer in Chinese Han population.

Hong Shaodong S Fang Wenfeng W Hu Zhihuang Z Zhou Ting T Yan Yue Y Qin Tao T Tang Yanna Y Ma Yuxiang Y Zhao Yuanyuan Y Xue Cong C Huang Yan Y Zhao Hongyun H Zhang Li L

Scientific reports 20141201

The predictive power of age at diagnosis and smoking history for ALK rearrangements and EGFR mutations in non-small-cell lung cancer (NSCLC) remains not fully understood. In this cross-sectional study, 1160 NSCLC patients were prospectively enrolled and genotyped for EML4-ALK rearrangements and EGFR mutations. Multivariate logistic regression analysis was performed to explore the association between clinicopathological features and these two genetic aberrations. Receiver operating characteristic ...[more]

PMID: 25434695

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Project description:BACKGROUND:A number of mutations in key oncogenes have been identified as important for the initiation and maintenance of lung adenocarcinoma (LAC). This study elucidated the prevalence and prognostic significance of mutations in the epidermal growth factor receptor gene (EGFR) and rearrangements in the anaplastic lymphoma kinase gene (ALK) in patients with surgically resected primary LAC. PATIENTS AND METHODS:We retrospectively analyzed 675 consecutive patients who underwent radical resection at a single institution. We concurrently analyzed mutations in EGFR and the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) by reverse transcription (RT)-PCR, and investigated ALK rearrangements by immunohistochemistry. LAC with or without various oncogenic mutations was studied for clinicopathological features and their association with disease-free survival (DFS) and overall survival (OS). RESULT:ALK rearrangements and EGFR mutations were detected in 75 and 312 patients, respectively, with coexistence in 5 cases. ALK rearrangements and mutations in EGFR and KRAS were mutually exclusive. Compared with patients with EGFR mutations, ALK rearrangements were more common in younger patients, and those with advanced tumors, lymph node metastases, and higher rates of postoperative adjuvant therapy. Histologically, EGFR mutations were more common than ALK rearrangements in patients with the acinar predominant subtype and the lepidic predominant subtype of LAC, whereas ALK rearrangements were more frequent in the solid predominant subtype with mucin production and invasive mucinous adenocarcinomas. ALK-positive patients had a significantly worse DFS than those with EGFR mutations and wild-type (WT) patients. The mean OS after surgical procedures was significantly longer in EGFR-mutated versus WT patients. No significant differences were found in patients with ALK-positive tumors compared with EGFR-mutated and WT patients. CONCLUSION:Clinicopathological features of LAC with ALK rearrangements differ from those of LAC with EGFR mutations. Patients with ALK rearrangements had a significantly worse DFS than those harboring EGFR mutations. Thus, ALK rearrangements are an adverse prognostic factor in surgically-resected LAC patients, while EGFR mutations are associated with a better prognosis.

Project description:The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P<0.05); never-smokers (42.3% vs 13.9% in smokers; P<0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P<0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites.

Dataset Information

A large-scale cross-sectional study of ALK rearrangements and EGFR mutations in non-small-cell lung cancer in Chinese Han population.

Publications

A large-scale cross-sectional study of ALK rearrangements and EGFR mutations in non-small-cell lung cancer in Chinese Han population.

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