Distribution of EGFR Mutations Commonly Observed in Primary Lung Adenocarcinomas in Pakistan as Predictors for Targeted Therapy

Purpose To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations. Patients and Methods In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1. Results Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations. Conclusion To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.

Download Full-text

Comparative Characteristics of Napsin A, TTF 1 and EGFR Mutation Expression in Mucinous Lung Cell Carcinomas

Folia Medica ◽

10.1515/folmed-2017-0020 ◽

2017 ◽

Vol 59 (2) ◽

pp. 174-182

Author(s):

Sylvia N. Genova ◽

Veselin T. Belovezhdov ◽

Stoyan N. Bichev ◽

Vladimir H. Danev

Keyword(s):

Salivary Gland ◽

Mutation Frequency ◽

Egfr Mutation ◽

Egfr Mutations ◽

Common Pattern ◽

Specificity And Sensitivity ◽

Napsin A ◽

Significant Difference ◽

Pcr Technology ◽

Lung Adenocarcinomas

AbstractBackground:Invasive mucinous lung adenocarcinomas are rare and account for 2%–10% of all lung adenocarcinoma cases. It is believed that Napsin A exhibits a weaker expression in mucinous adenocarcinomas compared with TTF1, but such correlation is still poorly researched.Aim:The aim of the study was to determine the frequency of mucinous to nonmucinous adenocarcinomas and compare specificity and sensitivity of monoclonal Napsin A with TTF1 in mucinous adenocarcinomas and define the frequency of EGFR mutations.Materials and methods:Eighty-four resected lung carcinomas were prospectively evaluated. All biopsies were analysed with p63, TTF1, monoclonal Napsin A, CK7, CK20 and CDX2 and were studied with real-time PCR technology.Results:In resected material we detected 49/84 (58.3%) adenocarcinomas and selected 21 mucinous adenocarcinomas out of 46 non-mucinous adenocarcinomas (45.6%). The most common pattern of mucinous adenocarcinomas is papillary - 24% and colloidal - 24%, followed by acinar - 19.2% and lepidic - 19.2%. mNapsin A was positive in 18/21 (85.7%) mucinous adenocarcinomas v/s 17/21 TTF1 positive (80.9%). EGFR mutations were detected in 3/21 cases with mucinous adenocarcinomas (14.3%): mucinous papillary, mucinous acinar and “salivary gland-like”.Conclusion:Our study demonstrates a high proportion of primary mucinous lung adenocarcinomas to primary non-mucinous adenocarcinomas. Sensitivity and specificity of mNapsin A and TTF1 did not show significant difference in pulmonary mucinous and non-mucinous adenocarcinomas, as mNapsin A gave greater sensitivity to mucinous adenocarcinomas. Our results indicate the same mutation frequency of EGFR in mucinous adenocarcinomas as mutation frequency detected in non-mucinous adenocarcinomas in the Bulgarian region.

Download Full-text

Clinical Features and Surgical Treatment of Synchronous Multiple Primary Lung Adenocarcinomas With Different EGFR Mutations

Frontiers in Oncology ◽

10.3389/fonc.2021.785777 ◽

2022 ◽

Vol 11 ◽

Author(s):

Rirong Qu ◽

Fan Ye ◽

Dehao Tu ◽

Yixin Cai ◽

Xiangning Fu

Keyword(s):

Clinical Features ◽

Mutation Rate ◽

Surgical Outcomes ◽

Clinical Characteristics ◽

Egfr Mutations ◽

Driver Gene ◽

Invasive Adenocarcinoma ◽

Significant Difference ◽

Multiple Primary ◽

Lung Adenocarcinomas

BackgroundWith the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA.MethodsMedical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated.ResultsA total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions >20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively.ConclusionsA high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis.

Download Full-text

Clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e20588 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e20588-e20588

Author(s):

Linping Gu ◽

Bei Zhang ◽

Ding Zhang ◽

Hong Jian

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

De Novo ◽

Egfr Mutations ◽

Genomic Profiling ◽

Small Cell Lung ◽

Genetic Characteristics ◽

Egfr Mutant ◽

Lung Adenocarcinomas ◽

Egfr T790m

e20588 Background: Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the resistance mechanism of EGFR tyrosine kinase inhibitors. However, the clinical course of transformed SCLC and the difference of genomic profiling between de novo SCLC patients and transformed SCLC patients are still poorly characterized. Methods: Patients from our hospital diagnosed with SCLC were enrolled retrospectively in this study, including de novo SCLC patients and SCLC patients transformed from EGFR-mutant lung adenocarcinomas. Genomic profiling was performed on formalin-fixed paraffin-embedded tumor samples by next generation sequencing (NGS). In statistical analysis, fisher ‘exact test was used. All tests were bilateral, with P<0.05 indicating significant statistical difference. Results: In total, 16 patients with SCLC transformed from EGFR-mutant lung adenocarcinomas and 230 de novo SCLC patients were included in our study. Transformed SCLC patients were more in younger (p=0.007), female (p<0.001) and non-smokers (p<0.001) than de novo SCLC patients. In transformed SCLC patients, 12 patients (75%) occurred SCLC transformation within 2 years after the lung adenocarcinomas diagnosis. Median transformation time was 20 months. During the treatment of adenocarcinomas, the overall response rate (ORR) was 75% and the median progression-free survival was 12 months. After the initiation of SCLC therapy, the ORR of 1st line chemotherapy was 40%. For the genomic profiling, EGFR mutations, including exon 19 deletion (56%), L858R (38%), and others (6%), were detected. 11 patients with acquired resistance were received EGFR T790M test, 82% of patients had acquired EGFR T790M mutation. 11 patients after transformation to SCLC had NGS test, 100% maintained their founder EGFR mutation, and other recurrent mutations included TP53, RB1 and EGFR amplification. Compared with the genetic alterations in de novo SCLC patients, TP53 mutations were significantly decreased (p=0.006) while EGFR mutations were significantly elevated (p<0.001) in transformed SCLC patients. However, no significant difference on RB1, ALK and ROS1 mutations were observed. Interestingly, a 60-year-old woman in our transformed SCLC cohort harbored EGFR 19 del mutant at allele frequency of 50.39%，she received osimertinib plus epirubicin/cyclophosphamide as 1st line treatment and reached partial response, with survival of 4 years to date. Conclusions: We demonstrated the clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC and found one patient still benefited from EGFR-TKI. Our study suggested that SCLC patients with EGFR mutation who transformed from lung adenocarcinoma may be potential benefit population using EGFR inhibitors.

Download Full-text

Clinical Utility of Target Selector™ ctDNA Testing: Detection of EGFR Mutations via Liquid Biopsy Enabled Targeted Therapy Selection for Patients with Advanced NSCLC

Journal of Cancer Science and Research ◽

10.4172/2576-1447.1000113 ◽

2018 ◽

Vol 03 (02) ◽

Author(s):

Veena M Singh ◽

Rodrigo Erlich ◽

Cecile Rose T Vibat

Keyword(s):

Targeted Therapy ◽

Liquid Biopsy ◽

Clinical Utility ◽

Advanced Nsclc ◽

Egfr Mutations ◽

Selection For

Download Full-text

Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.3224 ◽

2006 ◽

Vol 24 (11) ◽

pp. 1700-1704 ◽

Cited By ~ 147

Author(s):

DuyKhanh Pham ◽

Mark G. Kris ◽

Gregory J. Riely ◽

Inderpal S. Sarkaria ◽

Tiffani McDonough ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Receptor Gene ◽

Growth Factor Receptor ◽

Smoking History ◽

Egfr Mutations ◽

Epidermal Growth ◽

Former Smokers ◽

Never Smokers ◽

Lung Adenocarcinomas ◽

Exon 19

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

Download Full-text