Frequency Of Epidermal Growth Factor Receptor Mutations Research Articles

Common epidermal growth factor receptor mutations in north Indian patients with non-small cell lung carcinoma: evidence from real-time polymerase chain reaction.

Lung carcinoma was the ace cause of cancer deaths globally in 2022, with non-small cell lung carcinoma (NSCLC) accounting for 81% of the burden. Due to promising tyrosine kinase inhibitor (TKI) trials, NSCLC patients harboring epidermal growth factor receptor (EGFR) gene mutations are of interest. Our aim was to determine EGFR mutation prevalence in north India and its histologic and demographic correlations. We investigated the frequency of EGFR mutations in 40 patients with histologically confirmed NSCLC using real-time polymerase chain reaction. A 15% mutation frequency was observed in the study sample, involving 32 males and 8 females with a median age of 59 years. Squamous cell carcinoma (SCC) patients had only EXON20 (T790M, exon20 insertion) mutations, while adenocarcinoma patients had mutations in both EXON20 (T790M) and 21 (L858R) with mutation frequencies of 22% and 10%, respectively. 28% of the SCC patients were non-smokers, and 60% of these non-smokers had an EGFR mutation. South Indian and Asian studies have identified EXON19 (19-Del) and EXON21 (L858R) mutations as "common mutations" that account for nearly 80-90% of all mutations and respond well to TKIs. Interestingly, "common mutations" were found seldom in our study population, while the uncommon variants constitute 83% of all mutations, which we assume is due to diverse Indian genetics and ethnicity and co-existing signature mutations that involve the tyrosine kinase domain of EXON20. We suggest future genome-wide association studies to identify plausible genetic polymorphisms responsible for interethnic differences in EGFR mutation, which will contribute to better treatment and prevention of NSCLCs.

Molecular Testing for EGFR Mutation in Moroccan NSCLC Patients: CHU Hassan II-Fez Experience.

Epidermal growth factor receptor (EGFR) mutation screening in non-small cell lung cancer (NSCLC) is now used to guide treatment decisions to identify patients with EGFR positive mutations that predict response to EGFR tyrosine kinase inhibitors. This study aimed to explore with a prospective study the current testing practices and the predictive value of EGFR mutations in a series of 261 patients with NSCLC. EGFR mutation testing was conducted using 2 different assays: bidirectional Sanger sequencing of polymerase chain reaction (PCR) and real-time PCR on the Rotor-Gene Q instrument. Epidermal growth factor receptor mutation testing was performed for 261 patients with lung cancer. Exons 18 to 21 were successfully analyzed in 113 tumors by Direct sequencing and in 148 tumors by real-time PCR. The prevalence of positive EGFR-mutations in each method was 22.1% (N = 25) and 24.3% (N = 36), respectively (P = .3). In total, EGFR mutations were detected in 59 patients among 261 patients with NSCLC. A statistically significant association between female sex, nonsmoking history, nonsolid major pattern, and a higher EGFR mutation frequency. In this study, we investigated clinicopathological differences between tumors harboring exon 19del and those harboring L858R. We did not find any significant differences between the 2 mutations and gender or smoking features, interestingly, the prevalence of patients aged >60 years was significantly higher in the L858R group than in the exon 19del group (81.8% vs 55.8%, P = .05). A significant association was observed between exon 19 deletions and the papillary major pattern, but no correlation was detected between exon 21 mutation and any histological pattern. This prospective study documented the real-world clinical testing of EGFR mutation in Moroccan NSCLC patients. Our experience confirms the need to develop standards-based guidelines for the routine performance and evaluation of EGFR testing to improve clinical care for this subset of lung cancer. On the other hand, our study demonstrated that tumors with exon 19 deletions and L858R harbor specific clinicopathological features in NSCLC.

Frequency of EGFR mutation and EML4-ALK fusion genes in patients with non-small cell lung carcinoma

Lung cancer ranks among the top causes of mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for the majority of cases. Advances in genomics have identified potential biomarkers to predict therapeutic strategies in lung cancer. Despite the availability of targeted drugs such as tyrosine kinase inhibitors, a substantial proportion of patients still experience problems such as drug resistance. Mutations in genes like epidermal growth factor receptor (EGFR) and EML4ALK have already been established with altered clinical outcomes in NSCLC patients. With a focus on non-small cell lung cancer (NSCLC),the study was conducted at indraprastha apollo hospital in new delhi. With their informed agreement, 90 patients who were admitted between january 2012 and december 2015 and who had been diagnosed with fine-needle aspiration cytology (FNAC)/biopsy utilizing computed tomography (CT) guidance were included in the study. Excluded from the study were those receiving radiation therapy or chemotherapy concurrently. Information on age, gender, a thorough medical history, a history of smoking, and any additional co-morbidities were taken from medical records. Investigation of EGFR mutation and EML4-ALK gene fusion in NSCLC patients was done. Eleven (11% ) were positive and (89%) were negative for EGFR mutations. The positive cases were analyzed for exon 19 deletion and exon 21 (L858R) substitution and found positive for (60%) and (40%) of cases, respectively. Amongst 90 EGFR-negative patients, 4 (4.4%) had the EML4-ALK fusion gene, while 86 (95.5%) were negative for EML4-ALK. This study’s EML4-ALK fusion gene incidence was only (4%). Females have a higher occurrence of EGFR mutations than males (p=0.003) and the frequency of EGFR mutation was higher in non-smokers. The overall incidence of the EML4-ALK fusion gene was (4.44%) and was higher in patients below 60 years of age.

Advances of Molecular Targeted Therapy in EGFR-mutated Squamous Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is a prevalent tumour type in our country, with lung squamous carcinoma being a commonly observed NSCLC subtype besides lung adenocarcinoma. Epidermal growth factor receptor (EGFR) is a significant driver gene in lung cancer, and EGFR mutation frequency is considerably lower in lung squamous carcinoma in comparison to lung adenocarcinoma. Although targeted therapy against EGFR has demonstrated significant advancements in lung adenocarcinoma, while progress in lung squamous carcinoma has been relatively sluggish. This paper reviews recent studies on molecular targeted therapy for EGFR-mutated lung squamous carcinoma and summarises the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in treating squamous carcinoma of the lung, in order to provide a reference for treating patients with EGFR-mutated squamous carcinoma of the lung. .

Bilateral diffuse metastases in advanced lung adenocarcinoma harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKIs.

Bilateral diffuse metastatic lung adenocarcinoma (BLDM-LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co-mutation characteristics of BLDM-LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR-yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non-small-cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM-LUAD. In order to analyze the survival outcomes of BLDM-LUAD patients harboring EGFR mutations who were treated with EGFR-TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR-TKIs treatment were adjusted using propensity score-matching (PSM). The Kaplan-Meier survival curves and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The co-mutation characteristics of BLDM-LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first-line treatment of EGFR-TKIs were successfully matched. BLDM-LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM-LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co-mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia-mutated (ATM) (7.4%) and mesenchymal-epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM-LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKI.

Rapid and reliable testing for clinically actionable EGFR mutations in non-small cell lung cancer using the IdyllaTM platform: a real-world two-center experience in Greece

ABSTRACT Background Limited information exists on epidermal growth factor receptor (EGFR) molecular epidemiology in Greece. Next-generation sequencing (NGS) is the recommended method for EGFR genotyping in NSCLC. The Idylla Biocartis platform is a fully automated system for actionable EGFR mutation detection. Research design and methods We describe the prevalence of EGFR mutations in NSCLC patients in two high-volume clinical centers in Greece and compare key methods used for their determination. Eight hundred and fifty-seven FFPE samples from NSCLC patients were tested for EGFR mutations at University of Crete (UoC; n = 324) and at Evangelismos Hospital, Athens (Evangelismos; n = 503). Results The prevalence of EGFR mutations was 11.1% in the whole cohort (11.5% in non-squamous). The detection rate was 11.0% by NGS, 9.8% by Sanger and 11.3% by Idylla for the whole cohort (12.0% in non-squamous). The agreement between Idylla and Sanger was 93.2%. A targetable EGFR mutation was detected in 10.0% using tissue NGS alone, and in 16.0% using concurrent Idylla ctEGFR testing. Conclusion The frequency of EGFR mutations was as expected for a Caucasian population. The Idylla EGFR test performance is comparable to reference methods and with a shorter TAT. Adding a concurrent plasma Idylla test to tissue NGS testing increases the detection rate of EGFR mutations in NSCLC.

A problem with clinical T factor in the 8th TNM edition: Prognosis and EGFR mutation status of small sized lung cancers with difficulty to measure the diameter of solid component in part-solid tumor

ObjectiveClinical T factors in the 8th TNM classification of lung cancer have a practical problem. In some cases, it is difficult to measure the size of the solid components in part-solid tumors, and the classification of these tumors is controversial. MethodsWe evaluated 590 resected cT1N0M0 stage IA non-small-cell lung cancers based on the 7th edition between 2009 and 2012. Tumor and solid component diameters were measured using thin-section computed tomography (CT). We defined tumors with difficulty in measuring the size of the solid components as lung cancers with scattered or mixed consolidation (LCSMCs). LCSMCs were observed in 79 (13.4%) patients. Other tumors were classified as cTis, cT1mi, cT1a, cT1b, and cT1c, according to the 8th edition. We compared prognosis and epidermal growth factor receptor mutations (EGFRm) status of LCSMCs with those of cT1a, cT1b, and cT1c. ResultsThe difference in overall survival (OS) among cT1a, cT1b, and cT1c was significant (5-year-OS: 96.9% vs. 76.8% vs. 65.0%). There was no significant difference in prognosis between LCSCs and cT1a (5-year-OS: 92.4% vs. 96.9%). A significant difference was observed in the frequency of EGFRm between cT1a, cT1b, and cT1c (52.4%, 42.4%, and 29.8%). The incidence of EGFRm in LCSMCs was 54.8% and there was no significant difference between LCSMCs and cT1a. ConclusionsThe prognosis and frequency of EGFRm in LCSMCs were close to those in cT1a. As we cannot measure the diameter of the solid component in subsolid lung cancers, it may be appropriate to classify these tumors as cT1a tumors.

Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.

The absence of thyroid transcription factor 1 (TTF-1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF-1 expression on the clinical response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD. The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed. A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF-1-negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF-1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF-1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF-1. Patients lacking TTF-1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression-free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR-TKIs compared to the TTF-1-positive patients with EGFR mutations. Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.

Performance of Ultra-Rapid Idylla™ EGFR Mutation Test in Non-Small-Cell Lung Cancer and Its Potential at Clinical Molecular Screening.

The Idylla™ EGFR Mutation Test is an ultra-rapid single-gene test that detects epidermal growth factor receptor (EGFR) mutations using formalin-fixed paraffin-embedded specimens. Here, we compared the performance of the Idylla EGFR Mutation Test with the Cobas® EGFR Mutation Test v2. Surgically resected NSCLC specimens obtained at two Japanese institutions (N = 170) were examined. The Idylla EGFR Mutation Test and the Cobas EGFR Mutation Test v2 were performed independently and the results were compared. For discordant cases, the Ion AmpliSeq Colon and Lung Cancer Research Panel V2 was performed. After the exclusion of five inadequate/invalid samples, 165 cases were evaluated. EGFR mutation analysis revealed 52 were positive and 107 were negative for EGFR mutation in both assays (overall concordance rate: 96.4%). Analyses of the six discordant cases revealed that the Idylla EGFR Mutation Test was correct in four and the Cobas EGFR Mutation Test v2 was correct in two. In a trial calculation, the combination of the Idylla EGFR Mutation Test followed by a multi-gene panel test will reduce molecular screening expenses if applied to a cohort with EGFR mutation frequency >17.9%. We demonstrated the accuracy and potential clinical utility of the Idylla EGFR Mutation Test as a molecular screening platform in terms of turnaround time and molecular testing cost if applied to a cohort with a high EGFR mutation incidence (>17.9%).

Molecular epidemiology and clinical characteristics of epidermal growth factor receptor mutations in NSCLC: A single-center experience from India.

The genetic profiling of non-small cell lung cancer (NSCLC) has contributed to the discovery of actionable targetable mutations, which have significantly improved outcomes in disease with poor prognosis. Molecular epidemiological data of driver mutations in Indian populations have not been extensively elaborated compared to western and eastern Asian NSCLC populations. This study assessed the prevalence and clinical outcomes of EGFR (epidermal growth factor receptor) mutations among the Indian NSCLC cohort in South India. Retrospective analysis of 2,003 NSCLC patients who had undergone EGFR mutational analysis from 2013 to 2020 was performed. Clinical analysis was performed for 141 patients from 2013 to 2017 using Kaplan-Meier and Chi-square methods. Descriptive and survival statistics were performed using IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. EGFR-sensitizing mutations were detected in 41.6% (834/2003) in the study cohort with compound mutations detected in 7.55% (63/834) of EGFR-positive cases. A significant relationship with regard to female gender and EGFR mutation status (P <.001) was observed. Exon 18 G719X (8.7%) mutations and exon 20 T790M point mutation (3.1%) were the most frequently isolated uncommon EGFR mutations. In the clinical cohort, EGFR mutations were detected at a significantly higher prevalence in females (P =0.002) and never-smokers (P < 0.001). EGFR mutation demonstrated a significant relationship with regard to brain metastasis (P = 0.011). EGFR mutated individuals had significantly longer median overall survival compared to EGFR wild type (26 months vs. 12 months, P = 0.044). We reports the highest number of EGFR mutation analysis performed from India and mutational analysis indicated a loco-regional variation in India with regard to EGFR mutation frequency and its subtypes.

Higher Prevalence and Poorer Prognosis of EGFR Mutant Lung Adenocarcinoma in US Hispanics

Introduction: Activating mutations in Epidermal growth factor receptor (EGFR) occur in approximately 15% White, 40-50% of Asian and 15% of Black patients with lung adenocarcinoma. However, its prevalence in the nearly 60 million U.S. Hispanics/Latinos has not been well characterized. Herein we evaluate EGFR mutation frequency in U.S. Hispanic/Latino patients with lung adenocarcinoma at an academic institute serving a large multi-ethnic area. Methods: We queried our prospective database (2015-2019) for lung adenocarcinoma patients who underwent surgical resection and had routine mutational analysis by a targeted gene panel. We identified 768 patients and were able to stratify 668 patients by self-identified race/ethnicity. We compared demographics (chi-square) and survival (Kaplan-Meier). Results: From 2015-2019, 668 patients met inclusion criteria and were evaluated for incidence of common targetable EGFR mutations. EGFR mutations were present in 30% of all patients with Hispanics/Latino experiencing an incidence of 35%, significantly more than non-Hispanic White patients, p=0.019. Overall survival at 3 years was not significantly different amongst racial/ethnic groups. However, in patients with EGFR mutations, 3-year overall survival was significantly worse in Hispanic/Latino patients in comparison to non-Hispanic White patients (62% vs 96%, p=0.021). There was no difference in the pathologic stage or surgical procedure amongst racial/ethnic groups. Discussion: Approximately one-third of U.S. Hispanics with lung adenocarcinoma displayed EGFR mutations which were associated with decreased overall survival compared to White and Asian patients. Increasing mutational analysis and investigation of biological differences of this growing ethnic group is essential for optimal targeted treatment strategies as well as in the design of future clinical trials.

Investigation of EGFR and ALK mutation frequency and treatment results in advanced non-small cell lung cancer.

Lung cancer has opened a new era in cancer treatment by elucidating the tumor's molecular structure and identifying the targetable mutations. Identifying the targeted mutations in lung cancer constitutes one of the main steps of treatment planning. The frequency of EGFR (epidermal growth factor receptor gene) and ALK (anaplastic lymphoma kinase gene) mutations in non-small cell lung cancer (NSCLC) also varies in populations depending on ethnicity, gender, smoking, and histopathological subtype. In general, limited data are available regarding the frequency and regional distribution of these mutations in the Turkish population. Our study aimed to determine the frequency of EGFR and ALK mutations in patients with advanced-stage NSCLC and compare the clinical characteristics, treatment, and survival results of cases with mutations with the group without mutations. In our study, 593 patients with advanced-stage NSCLC diagnosis and mutational analyses were evaluated retrospectively. Demographic characteristics, tumor stages (tumor, node, metastasis, TNM), EGFR and ALK analysis results, treatments applied, and survival of the cases were recorded. EGFR analysis, exon 18, 19, 20, and 21 mutations were studied with real-time PCR (RT-PCR) Rotor-Gene system from patients' samples. For ALK analysis, the ALK Break Apart kit (Zytovision GmbH; Germany) was used with the fluorescent in situ hybridization (FISH) method. In our study, EGFR mutation was detected in 63 patients (10.6%) and ALK mutation in 19 patients (3.2%) out of 593 patients. EGFR mutation was observed more frequently in women and non-smokers (P = 0.001, P = 0.003). No correlation was found between the presence of EGFR mutation and metastases regions and recurrence (P > 0.05). ALK mutation was observed more frequently in non-smokers and females (P = 0.001, P = 0.003). Patients with ALK mutations were younger than other groups (P = 0.003). There was also no significant relationship between ALK mutation and metastates regions and recurrence after treatment (P > 0.05). Patients with EGFR or ALK mutations had a longer life span than other cases (P = 0.474). Those who had ALK mutations and received targeted therapy had a longer average life expectancy (P < 0.05). No difference was observed in those who had EGFR mutations and received targeted treatment in terms of survival (P > 0.05). In our study, conducted in the Aegean region of Turkey, the positivity rates of EGFR and ALK mutations were found to be at similar rates with the Caucasian race across the world. EGFR mutation was more common in women, non-smokers, and patients with adenocarcinoma histology. ALK mutation was also detected more frequently in younger patients, women, and non-smokers. Patients with EGFR and ALK mutations had a longer life expectancy than those without the mutation. It was observed that testing patients diagnosed with advanced-stage NSCLC for genetic mutations of the tumor in the first step of the treatment and initiating treatment in patients with mutations provided a significant survival advantage.

Frequency of EGFR mutations in lung adenocarcinoma patients - A study from tertiary cancer center of South India.

Epidermal growth factor receptor (EGFR) mutation analysis has become an important part of the initial workup of non-squamous non-small cell lung cancer (NS-NSCLC) patients. This study is attempted as South Indians population is comprised of ethnic groups with diverse genetic makeup and only very limited data on EGFR mutation is available from south India. A detailed understanding of EGFR mutation profile will help in better planning of treatment strategies and resource allocation. A retrospective analysis of EGFR mutation frequency in 350 patients diagnosed with adenocarcinoma of lung and its association with pathological characteristics was done. Out of 350 cases of pulmonary adenocarcinoma, within an age group ranging from 30 to 86 years. EGFR mutations were identified in 34.8% (n = 122) cases, out of which 35.24% (n = 43) were in non-smoker females (P = 0.001). Of the 14 cases with resistant type of EGFR mutations, nine were in smoker males and the remaining five in non-smoker females. Overall EGFR mutation frequency observed in our study was similar to other Indian studies. However, in our study, we observed that mutation in exon 21 was less frequent compared to other studies. A similar slightly increased frequency of rare mutations and double mutations were observed in our study. A detailed study of the molecular epidemiology of lung cancer and its association with different geographical zones of India is needed. This understanding will help in better planning of treatment strategies and resource allocation.

Utilisation Patterns and Treatment Outcomes of EGFR-Tyrosine Kinase Inhibitors in EGFR-mutant Advanced Lung Carcinoma in the Pakistani-Asian Population: A Real-world Data Study.

Data on the utilisation of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) and their clinical outcomes in a heterogeneous Pakistani-Asian population have not been previously reported. This manuscript presents the first account of the clinical outcomes of EFGR-TKIs in EGFR-mutant lung adenocarcinoma among Pakistani-Asians. A real-world data study was conducted on all advanced lung cancer patients harbouring EGFR-mutations from the cancer registry of Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. We identified three different patterns of the use of EGFR-TKIs (Groups 1, 2 and 3) that reflect the ground realities of cancer care and delivery in Pakistan. We also noted a significant proportion of patients (Group 4) without access to EGFR TKIs. We compared the objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) of each of the four groups and reported their toxicity profile. Within the limitations of a retrospective analysis, we saw differences in the frequency of EGFR mutations in this population. However, response rates and long-term outcomes of EGFR TKI therapy were comparable with the existing data. The overall use of EGFR TKIs led to a superior outcome in ORR, PFS and OS compared to chemotherapy alone; (77.8% vs. 50.0%, 16.3 vs. 10.7 months; P = 0.099; 85.6 vs. 25.9 months, respectively; P = 0.13). Except for modest differences, EGFR-mutant advanced lung adenocarcinoma outcomes among Pakistani-Asians are comparable to those of other populations.

Phenotypic and Genotypic Appraisal of Pulmonary Mucinous Adenocarcinoma: A Retrospective Study

Introduction: Lung cancer is the second most common cancer diagnosed in the world. According to GLOBOCAN 2020, it is approximately 11.4% of all malignancies and accounts for one in five cancer deaths worldwide. Several driver gene mutations are known in lung adenocarcinoma including Epidermal Growth Factor Receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog(KRAS), v-raf murine sarcoma viral oncogene homolog B1(BRAF), Human epidermal growth factor receptor2 (HER 2), anaplastic lymphoma kinase (ALK), Ros Protooncogene 1, Receptor Tyrosine Kinase (ROS1) and rearranged during transfection (RET). Among these, KRAS mutation has been classically defined as bearing a negative prognostic factor. They are described to have unfavourable survival rates as compared with KRAS wild- type tumours. However, its real significance remains controversial due to heterogeneity amongst studies. Aim: The aim of this study was to assess the histomorphology, immunophenotype, EGFR and KRAS mutation profile in invasive mucinous and mixed mucinous/non mucinous type lung carcinoma. Materials and Methods: This retrospective study was done at a tertiary cancer centre in the state of Kerala, South India to identify the frequency of EGFR and KRAS mutations in invasive mucinous or mixed mucinous/non mucinous type lung carcinoma diagnosed during the period June 2017 to March 2019. Immunohistochemical assays for CK7, CK20, TTF-1, Napsin-A, CDX-2 and p63 were done on all cases. EGFR mutation analysis for exons 18, 19, 20, 21 were done using ARMS PCR and KRAS mutation analysis for codons 12, 13, 61, 146 by Sanger sequencer. Descriptive statistics was used wherever applicable. Results: Out of a total of 290 patients of pulmonary adenocarcinoma during the two year study period, twelve cases (4.1%) were diagnosed as invasive mucinous or mixed mucinous/non mucinous types based on histomorphology and immunophenotype, on both lung tissue biopsies as well as material from metastatic sites. Of the twelve, nine (75%) were pure mucinous and three (25%) were mixed mucinous and non mucinous. All the twelve cases were subjected to molecular testing for both EGFR and KRAS. Three cases (25%) showed KRAS mutations in codon 12. EGFR mutation (TKI resistant T790M mutation) was found only in a single case which had a histology of mixed mucinous and non mucinous carcinoma and a coexistent mutation in KRAS (c12 G&gt;C) gene. Conclusions: Our study corroborates the described fact that pulmonary mucinous carcinoma differ from the conventional adenocarcinoma in terms of its histology, immunoprofile and molecular profile. KRAS mutation appears to be the main pathogenetic factor in this variant. In the current day practice, there is no demonstrable effective therapy for KRAS mutant lung adenocarcinoma and more trials are needed to identify newer mutations that can modify treatment outcomes.

Association of smoking status with non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor mutation.

Uncommon epidermal growth factor receptor (EGFR) mutations include single and complex mutations. However, the association of the smoking status of patients with uncommon and complex EGFR mutations remains unclear. This retrospective study evaluates the spectrum of uncommon EGFR mutations and investigates the influence of smoking status on the frequency of various uncommon EGFR mutations using a multi-institutional medical database. Between 2010 and 2019, 5,608 non-small cell lung cancer (NSCLC) patients were analyzed. EGFR mutations were detected in 3,155 (56.3%) patients. Among the 399 (12.6%) patients with uncommon mutations, 198 had single uncommon and 201 complex mutations, including 87 exon 20 insertions, 79 de novo T790M, 70 complex common, and 52 complex uncommon mutations. For comparison, we also included 402 patients with common EGFR mutations. The percentage of ever-smokers was significantly higher in patients with uncommon EGFR mutations than in patients with common EGFR mutations (25.8% vs. 17.4%, p = 0.005). Furthermore, the percentage of ever-smokers was higher in those with a complex mutation than in those with a single uncommon mutation (30.3% vs. 21.2%, p = 0.040). Among patients carrying uncommon EGFR mutations, ever-smokers had significantly more complex uncommon EGFR mutations than never-smokers (22.3% vs. 9.8%, p = 0.002). Among patients carrying G719X, L861Q, and S768I, ever-smokers tended to have complex EGFR mutations more frequently than never-smokers (64.7% vs. 28.7%, 50.0% vs. 18.7%, 88.9% vs. 81.2%, respectively). Our study demonstrates not only a comprehensive spectrum of uncommon EGFR mutations, but also a positive relationship between smoking status and uncommon EGFR mutation frequency, especially complex uncommon EGFR mutations. The results suggest that smoking contributes to the development of complex EGFR mutations.

EGFR Mutation-Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis.

The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non-small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemoradiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status. We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern. Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation. Patients with EGFR mutation-positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.

Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing.

BackgroundActivating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR–tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations.MethodsWe examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response.ResultsEGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation–positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases.ConclusionsAlthough PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.

The prognostic impact of lung adenocarcinoma predominance classification relating to pathological factors in lobectomy, the Japanese Joint Committee of Lung Cancer Registry Database in 2010

ObjectiveWe studied the prognosis and clinicopathological background of lung adenocarcinoma predominance among patients who underwent lobectomy using data from the Japanese Joint Committee of Lung Cancer Registry.MethodsTwo thousand eight hundred sixty-three cases were extracted. Recurrence free survival (RFS) rates, overall survival (OS) rates and clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status were examined.ResultsMedian follow-up period was 65.5 months. Adenocarcinoma predominance was sub-grouped according to OS and RFS rate. In pathological stage I, 5-year RFS and OS rates were respectively 92.2% and 95.8% in group A (adenocarcinoma-in-situ + minimally invasive adenocarcinoma), 89.3% and 92.1% in group B (lepidic), 79.2% and 89.7% in group C (papillary + acinar + variants) and 69.0% and 79.0% in group D (solid + micropapillary). In pathological stage II + IIIA, they were, 43.6% and 72.4% in B, 39.5% and 66.9% in C and 31.0% and 53.7% in D. Group D showed significant worst outcome both in stage I and II + IIIA. Up stage rate from clinical stage I to pathological stage II + IIIA was 0.0%, 3.7%, 15.9% and 33.3%. The frequency of lymph-vessel, vascular, pleura invasion and positive EGFR mutation were 0.0%, 0.0%, 0.0% and 57.1% in group A, 15.6%, 10.0%, 12.1% and 55.1% in B, 36.6%, 31.8%, 29.7% and 44.9% in C, 50.2%, 57.8%, 38.9% and 21.3% in D. In group D, lymph-vessel, vascular and pleura invasion were most, EGFR mutation was least frequent not only in pathological stage I but also stage II + IIIA. In multivariate analysis, age, pathological stage, vascular invasion, and group D were independent factors affected RFS and OS.ConclusionLimited to lobectomy cases, solid + micropapillary was independent prognostic factor both in early and locally advanced stage. Its malignant degree was related to the frequency of pathological invasive factors and EGFR mutation status.

Molecular profile of non-small cell lung cancer in reunion Island

BackgroundIn recent years, the discovery of predictive biomarkers has enabled the development of targeted therapies that have improved the prognosis of patients with non-small cell lung cancer (NSCLC). No data are available at present on the molecular profile of NSCLC in Reunion Island, a French overseas department located in the Indian Ocean and characterized by an ethnically-mixed population. MethodThis observational, retrospective, and multicenter study included all patients who were diagnosed with NSCLC in Reunion Island during 2 years and whose tumor specimens were sent for molecular analysis at Bordeaux University Hospital. The aim of the study was to determine the molecular profile of NSCLC in the Reunionese population, including the frequency of epidermal growth factor receptor (EGFR) mutation. ResultsA total of 310 patients with NSCLC were screened for genetic mutations. Of these, 281 (91%) had adenocarcinoma, 207 (66%) were born in Reunion Island, 79 (25%) were never-smokers, and 109 (35%) were women. One hundred and seventy-eight (57%) patients had a genetic mutation. An EGFR mutation was detected in 69 patients (22%) of the 310 included patients. This mutation was detected in 23% of patients with adenocarcinoma, 40% of women, 55% of never-smokers, and 23% of patients born in Reunion Island. ConclusionThe frequency of EGFR mutation is high in the Reunionese population. This frequency is similar to that reported in Asia and may be explained by the history of migrations and ethnic mixing in Reunion Island. These findings suggest complex interactions between genetic and environmental factors in the carcinogenesis of NSCLC.