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

Pan, Yunjian; Zhang, Yang; Li, Yuan; Hu, Haichuan; Wang, Lei; Li, Hang; Wang, Rui; Ye, Ting; Luo, Xiangyang; Zhang, Yiliang; Li, Bin; Cai, David; Shen, Lei; Sun, Yihua; Chen, Haiquan

doi:10.1016/j.lungcan.2014.02.007

Cited by 191 publications

(145 citation statements)

References 19 publications

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“…Some studies recently reported the clinicopathologic features of RET rearrangements. 15,21,22 Our study also showed similar results in that patients with RET fusion-positive tumors were younger in age (median age, 55 vs 64 years; P ¼ 0.002), never-smokers (P ¼ 0.010) and early T stage (Po0.001) compared with patients with RET fusion-negative lung adenocarcinoma. However, there was no statistically significant difference in the N stage.…”

Section: Se Lee Et Alsupporting

confidence: 75%

“…20 Since the initial report of RET rearrangements in lung adenocarcinoma by Ju et al 10 in 2012, about 100 cases have been described in the literature. 6,21,22 Our study revealed that 16% (15 out of 94) of EGFR À /KRAS À /ALK À (triple-negative) lung adenocarcinomas harbored RET rearrangement. This prevalence was higher than that of the entire adenocarcinoma cohort because we screened the triple-negative cohort.…”

Section: Discussionmentioning

confidence: 70%

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Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

et al. 2015

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The success of crizotinib in ALK-positive patients has elicited efforts to find new oncogenic fusions in lung cancer. These efforts have led to the discovery of novel oncogenic fusion genes such as ROS1 and RET. However, the molecular and clinicopathologic characteristics associated with RET or ROS1 fusion, compared with ALK fusion-positive lung cancer, remain unclear. We accordingly analyzed the clinicopathologic characteristics of RET-and ROS1-fusion-positive lung adenocarcinomas. We further performed immunohistochemistry and fluorescence in situ hybridization analysis (FISH) in 15 cases of RET and 9 cases of ROS1 fusion tumors by identified NanoString's nCounter screening. RET fusion-positive patients were younger in age, never-smokers, and in early T stage; ROS1 fusion-positive patients had a higher number of never-smokers compared with patients with quintuple-negative (EGFR À /KRAS À /ALK À /ROS1 À /RET À ) lung adenocarcinoma. Histologically, RET and ROS1 fusion tumors share the solid signet-ring cell and mucinous cribriform pattern, as previously mentioned in the histology of ALK fusion tumors. Therefore, it can be presumed that fusion gene-associated lung adenocarcinomas share similar histologic features. In immunohistochemistry, the majority of 15 RET and 9 ROS1 fusion-positive cases showed positivity of more than moderate intensity and cytoplasmic staining for RET and ROS1 proteins, respectively. In FISH, the majority of RET and ROS1 rearrangement showed two signal patterns such as one fusion signal and two separated green and orange signals (1F1G1O) and an isolated 3 0 green signal pattern (1F1G). Our study has provided not only characteristics of fusion gene-associated histologic features but also a proposal for a future screening strategy that will enable clinicians to select cases needed to be checked for ROS1 and RET rearrangements based on clinicohistologic features.

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Section: Se Lee Et Alsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 70%

Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

et al. 2015

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“…Amplified products were analyzed by direct dideoxynucleotide sequencing. ALK, RET, ROS1, and FGFR fusions were analyzed by qRT-PCR plus RT-PCR and confirmed by FISH as we had previously reported [13][14][15][16]. PCR products were directly sequenced in forward and reverse directions.…”

Section: Mutation Analysesmentioning

confidence: 99%

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

et al. 2016

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The aim of this present investigation was to evaluate the clinicopathologic characteristics, oncogenic drivers, and prognosis of former smokers with non-smallcell lung cancer (NSCLC), and to compare them with those of the current and never smokers. This investigation was a single-institution retrospective study of 2289 NSCLC patients, who were classified as former, current, or never smokers. A collection was made of the clinicopathological characteristics, spectra of wellidentified driver genes and survival rates. The survival rates were compared using log-rank test, and independent prognostic factors, identified using Cox regression analysis. Of 2289 NSCLC patients, 257 (11.2%) were former smokers; 868 (37.9%), current smokers; and 1164 (50.9%), never smokers. Compared with the current, the former were characterized by older age at diagnosis (64.3y vs. 59.9y; P < 0.001), earlier TNM stage (stage I, 47.9% vs. 39.5%; P = 0.017), fewer solid predominance in adenocarcinomas (16.2% vs. 29.5%; P = 0.005), and more EGFR mutation (33.2% vs. 20.7%; P < 0.001) but less KRAS mutation (6.7% vs. 11.9%, P = 0.041). No statistically significant survival differences were observed between the former and current. However, the light former smokers presented favorable overall survival when compared with the light current and heavy former or current (the light former vs. the heavy former, P = 0.028; the light former vs. the light current, P = 0.048; and the light former vs. the heavy current, P = 0.048). Our findings suggest that the former smokers with NSCLCs can have distinctive clinicopathologic characteristics, oncogenic drivers, and prognosis, and they, especially the light former, can benefit from smoking cessation. Cancer Medicine Open Access 2118

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“…Finally, 9 studies including 6,899 patients were qualified for our meta-analysis. [10][11][12][20][21][22][23][24][25] Main features of 9 eligible studies were summarized in Table 1. The median age was reported in 7 studies and the average is 61.4.…”

Section: Study Characteristicsmentioning

confidence: 99%

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Chen

Wang

Xie

et al. 2015

Cancer Biology & Therapy

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(2015) The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis, Cancer Biology & Therapy, 16:7, 1019-1028, DOI: 10.1080/15384047.2015 Purpose. The RET fusion gene is a novel oncogene observed in a subset of NSCLC in recent years. Nevertheless, the results of epidemiological studies concerning the gene remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of RET fusion gene with demographic and clinicopathological features of NSCLC. Methods. PubMed, Embase, and Web of Science databases were searched to identify eligible studies. The association of RET fusion gene occurrence with gender, age, smoking status, histology type and tumor stage were analyzed in metaanalysis. Subgroup analysis according to patients' location (Asian and non-Asian) was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the correlation. Results. Nine studies with a total of 6,899 NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion gene were detected. The RET fusion gene was identified at significantly higher frequencies in female (OR D 0.55, 95%CI D 0.35-0.85) than male patients and in young (<60 ) patients (OR D 0.43, 95%CI D 0.19-0.99) than old patients ( 60 ), particularly in patients from Asian. A significant higher frequency was also identified in non-smokers (OR D 0.28, 95% CI D 0.16-0.49), and in patients with lung adenocarcinomas (OR D 3.59, 95%CI D 1.50-8.56). Additionally, no association between RET fusion gene and the TNM stage of tumor was observed. Conclusion. RET fusion gene occurred predominantly in Asian females with younger age, in non-smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients might be good candidates for personalized diagnostic and therapeutic approaches.

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

Cited by 191 publications

References 19 publications

Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

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