scholarly journals Morphological and Genetic Heterogeneity of Synchronous Multifocal Lung Adenocarcinoma in a Chinese Cohort

2020 ◽  
Author(s):  
Donglin Zhu ◽  
Dan Cao ◽  
Minghong Shen ◽  
Jinghuan Lv
Keyword(s):  
Lung Cancer ◽  
Primary Lung Cancer ◽  
Gene Mutations ◽  
Tumor Location ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Additional Tool ◽  
Molecular Features ◽  
Pathologic Features ◽  
Genotypic Analysis

Abstract Background: Synchronous multifocal lung cancer (SMLC) is seen with increasing frequency in clinical practice globally. Because of innate variation in clinical management and outcome, it is vital to distinguish properly between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Methods: We have collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumors were included in our study. The pathological features presented by these cases were analyzed, including tumor location, tumor size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We undertook molecular testing of nine driver oncogenes associated with lung cancer, including EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. Results: According to Martini-Melamed classification and refined standard, 8 and 17 cases were considered as SMPLC respectively. Gene mutations were identified in 18 tumors (36%). There were 12 patients had different gene mutations. Conclusions: We demonstrate that conventional morphological assessment is not sufficient to establish clearly the clonal relationship of SMPLC. Instead the evaluation of histological subtypes, including non-mucinous adherent components, is required. Multiplex genotypic analysis may also prove a useful additional tool.

scholarly journals Morphological and genetic heterogeneity of synchronous multifocal lung adenocarcinoma in a Chinese cohort

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Donglin Zhu ◽  
Dan Cao ◽  
Minghong Shen ◽  
Jinghuan Lv
Keyword(s):  
Lung Cancer ◽  
Primary Lung Cancer ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Driver Gene ◽  
Molecular Testing ◽  
Additional Tool ◽  
Molecular Features ◽  
Pathologic Features ◽  
Genotypic Analysis

Abstract Background Synchronous multifocal lung cancer (SMLC) is diagnosed with increasing frequency in clinical practice globally. Due to innate variation in clinical management and outcome, it is vital to properly distinguish between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Our objective was to evaluate the diagnostic value of histological morphologic features and driver gene mutations in SMLC classification. Methods We collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumours were included in our study. The pathological features that were presented by these patients were analysed, including the tumours location, tumours size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We conducted molecular testing of nine driver oncogenes that are associated with lung cancer, namely, EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. Results According to the Martini-Melamed classification and refined standard, 8 and 17 patients, respectively, were considered to have SMPLCs. Gene mutations were identified in 18 tumours (36%). Twelve patients had different gene mutations. Conclusions We demonstrate that conventional morphological assessment is not sufficient to clearly establish the clonal relationship of SMPLCs. Instead, the evaluation of histological subtypes, including nonmucinous adherent components, is required. Multiplex genotypic analysis may also prove to be a useful additional tool.

scholarly journals Cell-free DNA From Pleural Effusion Samples: Is It Right for Molecular Testing in Lung Adenocarcinoma?

2021 ◽  
Vol 27 ◽  
Author(s):  
Attila Mokánszki ◽  
Emese Sarolta Bádon ◽  
Anikó Mónus ◽  
László Tóth ◽  
Nóra Bittner ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Gene Mutations ◽  
Molecular Testing ◽  
Alternative Source ◽  
Cell Free Dna ◽  
Molecular Features ◽  
Free Dna ◽  
Mutational Status ◽  
Therapeutic Decisions

Pathogenic molecular features gained specific significance in therapeutic decisions in lung carcinoma in the past decade. Initial and follow up genetic testing requres appropriate amounts and quality of tumor derived DNA, but tumor sampling, especially for disease monitoring is generally limited. Further to the peripheral blood (PB), samples from pleural fluid, accumulating in diverse lung processes might serve as an alternative source for cell-free DNA (cfDNA) for genetic profiling. In our study, cfDNA isolated from the pleural effusion and from the PB, and genomic DNA (gDNA) obtained from tissue/cellular samples were analyzed and compared from altogether 65 patients with pulmonary disease, including 36 lung adenocarcinomas. The quantity of effusion cfDNA yield appeared to be significantly higher compared to that from simultaneously collected PB plasma (23.2 vs. 4.8 ng/μl, p < 0.05). Gene mutations could be safely demonstrated from the effusion cfDNA fraction obtained from adenocarcinoma patients, 3/36 EGFR, 9/36 KRAS and 1/36 BRAF gene variants were detected. In this series, 9/13 samples showed an effusion+/plasma-mutational status, while only 1/13 samples presented with the opposite findings (effusion-/plasma+). gDNA analysis from sediment cell blocks from the identical effusion sample was surprisingly ineffective for lung adenocarcinoma profiling due to the low DNA yield. In conclusion, the cell free supernatant of pleural effusions appears to concentrate cancer derived cfDNA and seems to be particularly suitable for serial genotyping of pulmonary adenocarcinoma.

Lung Cancer in 2013: State of the Art Therapy for Metastatic Disease

2013 ◽  
pp. 339-346
Author(s):  
Frances A. Shepherd ◽  
Paul A. Bunn ◽  
Luis Paz-Ares
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Poor Performance ◽  
Initial Therapy ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Molecular Features ◽  
Platinum Doublet

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor ( EGFR) and ALK should be performed in all patients before therapy. Platinum doublet chemotherapy may be considered for “fit” patients who do not have a molecular driver genetic abnormality. Bevacizumab can be considered for addition to the doublet in patients with nonsquamous cancers who have no contraindications. A pemetrexed combination is considered only in nonsquamous histology. Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance. The tyrosine-kinase inhibitors (TKIs) may be continued until multisite, symptomatic progression. For patients initially treated with a platinum doublet, maintenance chemotherapy with pemetrexed, erlotinib, gemcitabine, or possibly docetaxel is an option with selection based on clinical features, histology, type of initial therapy, and response to first-line therapy.

NSCLC driver mutations in the Quebec population: Epidemiologic and clinical evaluation.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22159-e22159
Author(s):  
Wissam Saliba ◽  
Mustapha Ali Tehfe ◽  
Roula Albadine ◽  
Danh Tran-Thanh ◽  
Denis Soulieres ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Stage ◽  
Smoking History ◽  
Driver Mutations ◽  
Molecular Testing ◽  
Tobacco Exposure ◽  
Molecular Features ◽  
Pcr Rflp ◽  
Different Populations ◽  
Regional Disease

e22159 Background: Recent advances in lung cancer treatment embrace the recognition of molecular pathways implicated in its pathogenicity, paving the path to personalized therapies. We conducted a retrospective analysis to characterize the molecular features of the population treated for non-squamous non-small cell lung cancer (NS-NSCLC) in the province of Quebec. Methods: 622 patients with NS-NSCLC and adequate tumor blocks, treated at the CHUM between 2006 and 2008, were included. All samples were tested for ALK translocations (by IHC and FISH), EGFR classical exon 19 and 21 mutations by PCR (fragment analysis and qPCR) and for KRAS codon 12 and 13 mutations by mismatch PCR-RFLP. Molecular features were matched to demographic characteristics and clinical outcomes. Results: So far, complete results are available for 153 patients. Considering the amount of tumor tissue available, this population is largely represented by patients with local or loco-regional disease (n= 140, 91.5%). A minority of patients (10.3%) was never or light smokers (< 10 pack-yrs). Only 2 patients (1.3%) were of Asian descent. The following table depicts the outcomes of this cohort of patients segregated according to mutation status and extent of disease. Conclusions: ALK rearrangements were not identified in this unselected NS-NSCLC population characterized by localized disease and strong smoking history. ALK translocation prevalence in different populations is likely to be largely influenced by its tumor stage distribution, tobacco exposure and the use of selection criteria for molecular testing. An expanded cohort of patients will be presented at the meeting. [Table: see text]

The targetable mutation landscape of Chinese patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
Jun Li ◽  
Cuiyun Zhang ◽  
Jiuzhou Zhao ◽  
Zhizhong Wang ◽  
Bing Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Essential Information ◽  
Nsclc Patients

e13018 Background: In recent years, the prognosis of non-small cell lung cancer (NSCLC) patients has been substantially improved by targeted therapies against specific molecular aberrations, i.e. tyrosine kinase inhibitors (TKIs) for Epidermal Growth Factor Receptor ( EGFR) etc. Several genes have been suggested by NCCN guideline (v7.2017) to test for NSCLC patients, including EGFR, ALK, ROS1, BRAF, MET, RET, HER2 and KRAS. The aim of this study is to profile the landscape of actionable mutations in Chinese NSCLC patients. Methods: From 2015 to 2017 621 treatment naïve NSCLC patients enrolled in the affiliated cancer hospital of Zhengzhou University were included in this analysis. DNA was extracted from the FFPE biopsies of these patients and processed for target capture sequencing covering the exons and flanking splicing regions of the 8 genes suggested by NCCN guideline, as well as introns of ROS, ALK and RET. Results: In total, 593 out of the 621 NSCLC patients harbor one or more mutations in these 8 genes, accounting for 95.5% of all the cases. EGFR, ALK and HER2 are the top 3 mutants, with a frequency of 52%, 32% and 26% respectively. Genetic aberrations in BRAF, MET, ROS1, KRAS and RET occur in 22%, 18%, 16% and 14% of the patients. The most common variation is missense; T > G, C > T and C > A changes are more often observed than T > C, T > A and C > G; the median number of variants per sample is 2, ranging from 1 to 13. There are 418 mutations detected on EGFR, of which 206 (49.28%) are clinically relevant. EGFR L858R, Exon19 deletion, Exon20 insertion, G719, A750P were observed in 123 (29.43%), 43 (10.29%), 8 (1.91%), 6 (1.44%) and 6 (1.44%) cases respectively. Gene fusions were identified in 78 cases, and the EML4- ALK is the most common one occurred in 54 patients, other fusion genes include KIF5B- ALK (11) ， CCDC6- RET (4), CD74- ROS1 (4), EZR- ROS1 (2), ERC1- RET (1), , SDC4- ROS1 (1) and TCOF1- ROS1 (1). Conclusions: Target sequencing of the 8 genes suggested by NCCN guideline for NSCLC patients reveals essential information for designing personalized therapeutic regimen. Chinese patients, maybe other Asian countries also, may benefit more from this molecular testing, because of the high occurrence of actionable mutations.

scholarly journals Catalog of Lung Cancer Gene Mutations Among Chinese Patients

2020 ◽  
Vol 10 ◽  
Author(s):  
Xinying Xue ◽  
Idorenyin Asuquo ◽  
Lei Hong ◽  
Jie Gao ◽  
Zhouhuan Dong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Cancer Gene

scholarly journals Primary synchronous small and non-small cell lung cancer in the same lung lobe: A case report

2017 ◽  
Vol 87 (3) ◽  
Author(s):  
Anton Dzian ◽  
Fúčela Ivan ◽  
Huťka Zdenko ◽  
Szépe Peter
Keyword(s):  
Lung Cancer ◽  
Mediastinal Lymph Node ◽  
Small Cell Lung Carcinoma ◽  
Treatment Protocol ◽  
Primary Lung Cancer ◽  
Small Cell ◽  
Individual Treatment ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Synchronous multiple primary lung cancer (SMPLC) means tumours present at the same time, which are separate and have different histology. We present the case of a 66-year-old patient with a combination of small-cell lung carcinoma (SCLC) with adenocarcinoma in the same lobe with metastasis of SCLC in the mediastinal lymph node. This is a rare case. We performed a standard left upper video-assisted thoracoscopic lobectomy with mediastinal lymphadenectomy and adjuvant therapy targeted to SCLC was administered. Despite advances in imaging methods and diagnostic procedures in pneumology a diagnosis of SMPLC is often discovered only intraoperatively or accidentally during the histological examination. Actually, no guidelines exist for the treatment protocol of such cases. Multiple methods of management of SMPLC, mainly complete anatomical resection with lymphadenectomy combined with chemotherapy or radiotherapy should be adopted according to the histologic types, staging and molecular testing of the tumours. These rare cases of SMPLC require individual treatment and multidisciplinary approach. 

Comprehensive investigation of mutational features of adenocarcinoma in situ and invasive adenocarcinoma among Chinese lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
Chan Xiang ◽  
Yuchen Han ◽  
Wentao Fang ◽  
Haohua Teng ◽  
Shengnan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Adenocarcinoma In Situ ◽  
Braf Mutations ◽  
Invasive Adenocarcinoma ◽  
Detection Rates ◽  
Lung Cancer Patients ◽  
Exon 20

9051 Background: Lung adenocarcinoma (LUAD) is further classified into several histological subtypes with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) as the three major subtypes according to the extent of invasion. AIS has been considered as a precursor of IAC. Considering the significantly higher mutation burden among IAC tumors than AIS tumors, it seems likely that AIS tumors undergo a process of accumulating various somatic mutations to gain invasive ability. To understand the gene mutations involved in this transformation, we compared the mutational features of AIS and IAC tumors. Methods: This retrospective study included 2,769 Chinese patients diagnosed with stage 0-IIIA LUAD. Targeted sequencing was performed on tissue DNA isolated from 246 AIS tumors and 2,523 IAC tumors using 68 lung cancer-related genes (Lung Core, Burning Rock Biotech). Results: Analysis of mutation profiles revealed that mutation count was significantly lower for AIS ( P< 0.01) as compared to IAC tumors. Moreover, AIS tumors had significantly higher mutation detection rates for ERBB2 exon 20 insertion (20ins) ( P≤0.05), EGFR 20ins ( P≤0.05), non-V600E BRAF mutations ( P≤0.05), and MAP2K1 small insertion-deletion variants ( P≤0.05). These 4 gene mutations were grouped and referred to as AIS-like mutations for further analysis. Detection rates of AIS-like mutations were 54.9% for AIS tumors and 7.8% for IAC tumors. Patients with AIS-like mutation-positive AIS tumors were significantly younger than those with AIS tumors without AIS-like mutations ( P =0.018), while age were similar for IAC tumors with or without AIS-like mutations. Mutation count was similar between AIS tumors with or without AIS-like mutations. Interestingly, IAC tumors harboring AIS-like mutations had a significantly higher mutation count than those harboring known oncogenic drivers ( P= 0.045). Further investigation of the molecular profiles of IAC tumors harboring AIS-like mutations (n = 198) revealed the presence of various concurrent mutations in 8 genes including TP53 (39.4%), EGFR (non-20ins) (16.7%), RB1 (7.1%), PIK3CA (6.6%), MET (5.1%), ROS1 (4.0%), FLT3 (4.0%), and PTEN (3.5%), which were absent among AIS tumors, particularly those that harbor AIS-like mutations. In addition to TP53 (35.8%), PIK3CA (4.5%), and RB1 (4.0%), IAC tumors without AIS-like mutations (n = 2,324) had additional concurrent mutations in 2 other genes CDK4 (5.7%) and STK11 (3.9%) as compared to AIS tumors. Conclusions: Our data suggest that AIS-like mutations could be involved in the early stages of tumorigenesis by initiating the accumulation of other gene mutations that are required for the transformation of AIS tumors into IAC tumors. Our study contributes to a deeper understanding of the distinct gene mutations between AIS and IAC tumors among Chinese LUAD patients.

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