Chinese Lung Adenocarcinoma Patients Research Articles

ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: A comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features

BackgroundTo have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas. MethodsQuantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations. ResultsThere were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P=0.007), whereas all the 15 tumors harboring RET fusions were ≤3cm in diameter (P=0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P<0.001), cribriform pattern (P<0.001), signet ring cells (P<0.001) and hepatoid cytology (P<0.001). No significant difference in relapse-free survival (P=0.147) and overall survival (P=0.444) was observed between fusion-positive and fusion-negative patients. ConclusionsThis study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.

Analysis of EGFR, EML4-ALK, KRAS, and c-MET mutations in Chinese lung adenocarcinoma patients

ABSTRACTIntroduction: Mutation analysis of cancer driver genes is helpful for determining an optimal treatment strategy. We evaluated mutations in four driver genes, namely epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients from Hunan Province. Methods: We enrolled 110 lung adenocarcinoma patients in a single institution. EGFR and KRAS mutations were examined by direct sequencing, the EML4-ALK fusion gene was analyzed by fluorescence in situ hybridization, and c-MET amplification and c-Met protein expression were detected by quantitative PCR and immunohistochemistry, respectively. Results: EGFR and KRAS mutations were observed in 52.7% (58/110) and 3.6% (4/106) of patients, respectively. c-MET amplification was detected in 5.5% (6/110) of patients. In addition, 30% (33/110) of the cases expressed c-Met protein, including all of the patients harboring c-MET amplification. Ten percent (11/110) of patients harbored the EML4-ALK fusion gene, and the frequency of ALK rearrangement was higher than that of other cohort analyses involving patients from other regions in China. Almost all of these gene mutations were exclusive except that in two female non-smoking patients, who harbored an EGFR mutation and EML4-ALK rearrangement simultaneously. In total, 70% of patients in the study harbored one of the four gene mutations. Conclusions: Most Chinese lung adenocarcinoma patients harbor driver gene mutations, among which ALK rearrangements were more common in Hunan patients than in previously reported populations. Future clinical trials should be conducted to determine the safety and efficacy of drug combination targeting different driver mutations.

A prospective comparison study on EGFR mutations by direct sequencing and ARMS in completely resected Chinese non-small cell lung cancer with adenocarcinoma histology (ICAN).

1547 Background: ICAN study investigated EGFR mutation (M) status, clinical outcomes and recurrent risk factors in Chinese lung adenocarcinoma (ADC) patients (pts) after complete resection. Here we report analysis results for the overall EGFR M rate and the consistency between two EGFR M detecting methods, ARMS and PCR+direct sequencing (Seq). Methods: Pts were aged ≥18 years, with histological diagnosed lung ADC, and received surgical complete resection. Tumor sample EGFR M status (primary endpoint; positive [M+]) was determined according to clinical routine practice by whatever methods, including ARMS, Seq, liquid chip and mutant-enriched PCR. For the pts whose tissue was adequate after EGFR M testing by single method of either ARMS or Seq, the other method was applied. Results: Of 571 pts from 26 sites, 315 (55.2%) pts were EGFR M+. 420 pts’ tissues were tested by both ARMS and Seq. EGFR M+ rates were 58.1% and 54.5% respectively without statistical significance (p=0.0548). The total consistent rate (both M status and M types) between two methods was 76.7%. The following Table showed individual EGFR M types by two methods. Conclusions: The overall EGFR M+ rate in operable Chinese ADC was 55.2%. For resection samples, two common methods, ARMS and Seq, didn’t show statistical significance on EGFR M+ rate. Regarding EGFR M types, Seq found some rare mutations which ARMS kit could not detect, while ARMS seemed more sensitive for exon 20 and 21 mutations, especially for S768I and L861Q. Clinical trial information: NCT01106781. [Table: see text]