scholarly journals A Hospital-Based Study of EGFR and ALK Mutations in Patients with Lung Adenocarcinoma in Odisha

2021 ◽  
Vol 8 (11) ◽  
pp. 5795-5801
Author(s):  
Prasant Kumar Parida ◽  
Sashibhusan Dash
Keyword(s):  
Lung Adenocarcinoma ◽  
Indian Population ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
P Value ◽  
Anaplastic Lymphoma ◽  
Mutational Status ◽  
And Gender ◽  
Post Graduate Institute

Background: Patients with advanced non-small cell lung cancer (NSCLC) have considerably benefited from the molecular identification of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations and subsequent targeted therapy against these biomarkers. Few studies have been undertaken in the Indian population on the analysis of both EGFR and ALK mutations in lung adenocarcinoma cases. Aim and Objectives: The aim of this study was to determine the prevalence of EGFR and ALK mutations in lung adenocarcinoma patients, as well as to link mutational status with age, sex, and smoking history. Materials and Methods: This single hospital-based retrospective study was conducted at the Department of Medical Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, on histologically proven lung adenocarcinoma cases over a duration of two years from 01.08.2019 to 31.07.2021. Results: Out of a total of 164 cases, males comprised 89 (54.26%) of the 164 lung adenocarcinoma cases, while females comprised 75 (45.73%). EGFR mutations were found in 42 (26.75%) of the patients. In 9 cases, the ALK gene rearrangement was also determined to be positive (5.66%). In terms of EGFR and ALK mutations, there was no statistically significant relationship between patient age and gender. (P-value < 0.05). In our research, we found a link between nonsmokers and EGFR and ALK mutations. (P-value <0.05). The deletion of exon 19 (76.19%) was the most prevalent mutation, followed by the exon 21 L858R mutation (14.28%). Conclusion: This study was found to have a significantly higher rate of EGFR and ALK mutation in the Indian population with adenocarcinoma of lung compared to Western populations. To get the maximum benefit from targeted therapies, all patients of adenocarcinoma of the lung should have mutational testing for EGFR and ALK as part of a broad molecular pannel.

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

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.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Introduction: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co- mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR, KRAS, and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Driver gene alterations in lung adenocarcinoma: Demographic features of 2544 Chinese cases

2020 ◽  
Vol 35 (4) ◽  
pp. 44-50
Author(s):  
Mingming Hu ◽  
Tongmei Zhang ◽  
Yuan Yang ◽  
Nanying Che ◽  
Jie Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Age Groups ◽  
Growth Factor Receptor ◽  
Distinct Group ◽  
Egfr Mutations ◽  
Driver Gene ◽  
Driver Genes ◽  
Anaplastic Lymphoma ◽  
Arms Pcr

Background: To understand the association between driver gene variations and age and gender in patients with lung adenocarcinoma, we investigated mutations of the three most important driver genes—epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) fusion genes and c-ros oncogene 1 (ROS1)—in this retrospective cohort study. Methods: Patients newly diagnosed with lung adenocarcinoma who received EGFR and ALK/ROS1 gene tests at our hospital from September 2014 to May 2019 were enrolled. EGFR mutations and ROS1 fusions were examined by ARMS-PCR and ALK fusions by Ventana-D5F3 IHC assay and ARMS-PCR. Results: Of 2544 eligible subjects, 2539 accomplished EGFR mutation tests. The prevalence of EGFR mutations was 62.1% in females, higher than that of 45.1% in males. In females, the EGFR mutation rate remained relatively stable at 60%–65% across the six age groups. Females showed an increased distribution of EGFR L858R and a decreased distribution of exon 19 deletion (19Del) by age. The incidence of ALK/ROS-1 rearrangements decreased significantly with age. Conclusions: EGFR 19Del mutation is more prevalent in younger males and females, while L858R mutation is prevalent in older females. Both ALK and ROS1 rearrangements are more common in younger lung adenocarcinoma. The young lung adenocarcinoma population is a distinct group rich in targetable genomic alterations, and more research is needed to understand the mechanism.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2020 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR , KRAS , and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53 . Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR , KRAS , and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2020 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR , KRAS , and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53 . Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR , KRAS , and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals Frequency of EGFR Mutation and EML4-ALK fusion gene in Arab Patients with Adenocarcinoma of the Lung

2015 ◽  
Vol 6 (2) ◽  
pp. 19-23
Author(s):  
Hanan Ezzat Shafik ◽  
Mohamed Ashour
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egfr Mutation ◽  
Fusion Gene ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth

Abstract Introduction: Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. The frequency of epidermal growth factor receptor (EGFR) mutations is ethnicity-dependent, with a higher proportion in Asian populations than in whites, while the incidence of EML4-ALK (echinoderm microtubule-associated-protein like 4-anaplastic lymphoma kinase) fusion gene ranged from 1.6% to 16.4% in patients with NSCLC and these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. This study was conducted to determine the frequency of EGFR mutation and EML4-ALK fusion gene in our population and to determine the effect of different clinicopathological features on the expression of those mutations in patients with lung adenocarcinoma. Results: EGFR mutations were detected in approximately 33% of our patients in this series; the most frequently detected mutation was exon 19 deletion. EML4-ALK fusion gene was detected in 7.3% of patients. Conclusion: Our population exhibited the incidence of EGFR mutation approximately similar to that reported in East Asia and Japanese patients, higher than that recorded in USA, and Australia. However, more studies with larger patients’ numbers are needed to verify this finding.

scholarly journals Early serum tumor marker levels after fourteen days of tyrosine kinase inhibitor targeted therapy predicts outcomes in patients with advanced lung adenocarcinoma

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240736
Author(s):  
Hung-Jen Chen ◽  
Chih-Yen Tu ◽  
Kuo-Yang Huang ◽  
Chun-Ru Chien ◽  
Te-Chun Hsia
Keyword(s):  
Targeted Therapy ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Mutation Status ◽  
Anaplastic Lymphoma

Objective Image evaluation strategy for lung cancer patients has difficulty obtaining the appropriate quantity of diffuse lung nodules and bone metastases. The study was to demonstrate whether early variations in the levels of serum 4-tumor markers (4-TMs)(carcinoembryonic antigen [CEA], cancer antigen [CA]125, CA19-9, and CA15-3) after TKI targeted therapy were associated with treatment response in patients with lung adenocarcinoma. Methods Patients with stage IIIB-IV lung adenocarcinoma taking epidermal growth factor receptor (EGFR) TKIs or anaplastic lymphoma kinase (ALK) inhibitors were enrolled prospectively from June 2012 to February 2015. According to the variations of the percentage of change in 4-TM levels (4-TMpc), we divided patients into ascending (increases in 4-TMpc over the 7th- 14th day) and descending (decreases in 4-TMpc over the 7th- 14th day) groups. Results 184 patients were enrolled, and 89% had at least one of the pre-treatment evaluable TMs and were further analyzed. An excellent response to the TKI targeted therapy was accurately predicted in the descending group, as determined using receiver operating characteristic curve analysis (an area under the curve, 0.83). Multivariate Cox hazards model analyses demonstrated that the type of 4-TMpc and mutation status were the strongest predictors of progression-free survival (PFS)(descending versus ascending, hazard ratios [HR] 0.30, 95% confidence interval [CI], 0.19–0.47; sensitive mutation versus wide type, HR 0.30, 95% CI, 0.19–0.48). Conclusions Type of 4-TMpc 14 days after TKI targeted therapy is associated with an image response and PFS, without regarding mutation status, in patients with advanced lung adenocarcinoma.

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