Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p<0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p<0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p<0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.

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Evaluation of the fully automated Idylla EGFR Mutation Assay in Chinese patients with lung adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21716 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21716-e21716

Author(s):

Tian Qiu ◽

Li Junling ◽

Bo Zheng ◽

Jianming Ying

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Chinese Patients ◽

Egfr Mutations ◽

Arms Pcr ◽

Formalin Fixed Paraffin ◽

Ffpe Samples ◽

Formalin Fixed Paraffin Embedded ◽

User Friendly

e21716 Background: Epidermal growth factor receptor ( EGFR) mutation testing is nowadays an essential part of lung adenocarcinoma diagnosis. Its rapid detection is of utmost significance in order to ensure that patients receive timely and appropriate treatment. However, the current techniques for EGFR examination in China, ARMS-PCR and NGS, often take 3~7 days to deliver the final results. In contrast, the fully automated Idylla EGFR assay could detect 51 EGFR mutations directly from formalin-fixed, paraffin-embedded (FFPE) samples within 2.5 hours with < 2 minutes of hands-on time. The test has proven both accurate and robust among Caucasian lung adenocarcinoma patients but has never been clinically validated in Chinese patients. Methods: FFPE samples were retrospectively collected from 94 lung adenocarcinoma patients followed by EGFR testing using the Idylla system. Seventy-eight samples were also previously assessed with ARMS-PCR, 9 with NGS and 7 with both. In case of discordance, repeat testing was performed on the same tissue block with a third method. The sensitivity and specificity of the Idylla EGFR assay were evaluated against ARMS-PCR or NGS. Mutations beyond the scope of detection by the Idylla EGFR assay were not included in the analyses. Results: Of the 94 tumors enrolled, 77 were stage I-II. The Idylla system was consistent with ARMS-PCR or NGS for the EGFR mutational profiles of 92 tumors: 80 positive and 12 negative. Among the 2 cases of discrepancy, one was wild-type using Idylla but were found to harbor G719X/S768I using ARMS-PCR (and confirmed by NGS), while the other one carried L858R according to Idylla, as confirmed by ARMS-PCR, but was discovered to have an additional mutation L861Q using NGS. The Idylla EGFR test had a sensitivity of 97.6%, a specificity of 100% and an overall concordance of 97.9%. Conclusions: The Idylla system provides a rapid, accurate and user-friendly solution to EGFR characterization, especially in time-sensitive scenarios where special expertise and staff training could be a challenge.

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Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients with Lung Adenocarcinoma after Complete Resection: Results From the ICAN Study

JTO Clinical and Research Reports ◽

10.1016/j.jtocrr.2021.100257 ◽

2021 ◽

pp. 100257

Author(s):

Xue-Ning Yang ◽

Hong-Hong Yan ◽

Jun Wang ◽

Xiang-Yang Chu ◽

Zhi-Dong Liu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Real World ◽

Egfr Mutation ◽

Complete Resection ◽

Chinese Patients ◽

Survival Outcomes ◽

Mutation Status

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Correlation of EGFR mutation and predominant histologic subtype according to the new lung adenocarcinoma classification in Chinese patients

Medical Oncology ◽

10.1007/s12032-013-0645-1 ◽

2013 ◽

Vol 30 (3) ◽

Cited By ~ 38

Author(s):

Zhengbo Song ◽

Huineng Zhu ◽

Zhenying Guo ◽

Wei Wu ◽

Wenyong Sun ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Chinese Patients ◽

Histologic Subtype

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The Prognostic Value of Non-Predominant Micropapillary Pattern in a Large Cohort of Resected Invasive Lung Adenocarcinoma Measuring ≤3 cm

Frontiers in Oncology ◽

10.3389/fonc.2021.657506 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hua Zhang ◽

Wuhao Huang ◽

Chang Liu ◽

Giuseppe Giaccone ◽

Xiaoliang Zhao ◽

...

Keyword(s):

Lymph Node ◽

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Disease Free Survival ◽

Lymph Node Involvement ◽

Invasive Adenocarcinoma ◽

Node Involvement ◽

Invasive Lung Adenocarcinoma ◽

The Impact ◽

Micropapillary Pattern

The aim of this study was to analyze the influence of non-predominant micropapillary pattern in small sized invasive lung adenocarcinoma. A total of 986 lung adenocarcinoma patients with tumor size ≤3 cm were identified and classified according to the IALSC/ATS/ERS classification. Emphasis was placed on the impact of non-predominant micropapillary pattern on disease-free survival (DFS) and overall survival (OS). The relationship between lung adenocarcinoma subtype and lymph node involvement, EGFR mutation and KRAS mutation was also evaluated. A nomogram was developed to predict the probability of 3- and 5-year OS for these patients. The concordance index and calibration plot were used to validate this model. Among all 986 patients, the percentages of lymph node involvement were: 58.1, 50.0, 33.5, 21.4, 21.1, 10.9, 0, and 0% for micropapillary predominant, solid predominant, acinar predominant, papillary predominant, invasive mucinous adenocarcinoma (IMA), lepidic predominant, minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), respectively. The frequency of EGFR mutation in the cases of lepidic predominant, acinar predominant, MIA, micropapillary predominant, papillary predominant, solid predominant, IMA, and AIS were 51.1, 45.2, 44.4, 36.8, 29.3, 26.8, 8.3, and 0%, respectively. A non-predominant micropapillary pattern was observed in 344 (38.4%) invasive adenocarcinoma (IAC), and its presence predicted a poorer DFS (median: 56.0 months vs. 66.0 months, P <0.001) and OS (median: 61.0 months vs. 70.0 months, P <0.001). After propensity score matching, non-predominant micropapillary pattern retained its unfavorable effect on DFS (P = 0.007) and OS (P = 0.001). Multivariate analysis showed that non-predominant micropapillary pattern was identified as an independent prognostic factor for DFS (P = 0.003) and OS (P <0.001) in IAC. The nomogram showed good calibration and reliable discrimination ability (C-index = 0.775) to evaluated the 3- and 5-year OS. This retrospective analysis of patients with small sized IAC suggests the value of non-predominant micropapillary pattern to predict poor prognosis. A reliable nomogram model was constructed to provide personalized survival predictions.

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Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

Tumori Journal ◽

10.1177/03008916211005546 ◽

2021 ◽

pp. 030089162110055

Author(s):

Dashi Zhao ◽

Jun Fan ◽

Li Peng ◽

Bo Huang ◽

Yili Zhu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Alk Rearrangement ◽

Molecular Alterations ◽

Anaplastic Lymphoma ◽

Sporadic Cases ◽

Epidermal Growth ◽

Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

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Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders

Molecular Neurobiology ◽

10.1007/s12035-021-02377-y ◽

2021 ◽

Author(s):

Yi Zhang ◽

Tao Wang ◽

Yan Wang ◽

Kun Xia ◽

Jinchen Li ◽

...

Keyword(s):

Candidate Genes ◽

Neurodevelopmental Disorders ◽

De Novo ◽

Genetic Data ◽

Chinese Patients ◽

The Novel ◽

Mutational Spectrum ◽

Functional Variants ◽

Public Data ◽

Chromosomal Genes

AbstractNeurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.

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