|Year : 2017 | Volume
| Issue : 1 | Page : 305-307
Incidence and characteristics of Epidermal Growth Factor Receptor (EGFR) mutation in non-small-cell lung cancer (Adenocarcinoma histology): A report of 106 patients from Kolkata
K Chatterjee1, A Ray2, B Chattopadhyay3
1 Department of Radiotherapy, IPGMER & SSKM Hospitals, Kolkata, West Bengal, India
2 Department of Radiotherapy, Ruby General Hospital, Kolkata, West Bengal, India
3 Department of Clinical Research, DACRRI (under CCRH, Ministry of AYUSH, Govt. of India), Kolkata, West Bengal, India
|Date of Web Publication||1-Dec-2017|
Dr. K Chatterjee
Department of Radiotherapy, IPGMER & SSKM Hospitals, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
CONTEXT: Regional epidemiological data regarding the epidermal growth factor receptor (EGFR) mutation status in non-small-cell lung cancers (NSCLC) is an unmet need from the eastern part of India. AIMS: To report the incidence of EGFR mutation and its correlation with the phenotypical characteristics, in NSCLC patients from Kolkata. SUBJECTS AND METHODS: NSCLC patients, with adenocarcinoma histology, whose tissues had been tested for EGFR mutational status between March 2014 and February 2017, were considered for this study. The testing methods used were Real-time-based amplification refractory mutation system, polymerase chain reaction (ARMS PCR), PCR and gene sequencing, and cell-free DNA (CTDNA). Clinical characteristics and treatment details were collected from the patient's medical records in a de-identified manner. STATISTICAL ANALYSIS USED: Data were analyzed using simple descriptive statistical methods. RESULTS: Between March 2014 and February 2017, 108 samples were tested and two were deemed inadequate for reporting. Of the remaining 106 patients, 65 (61.3%) were males, and 41 (38.6%) were females. Median age was 56 years (42–72), 59 years for males and 52 years for females. 73.6% were nonsmokers. 87.7% tests were done using the real-time ARMS-PCR; 9.4% underwent PCR and gene sequencing and 2.8% using CT-DNA. Of 106 patients, 35 (33%) patients were found to be EGFR mutation positive. Ratio of male:female was 16 (45.7%):19 (54.3%). Ratio of nonsmoker: smoker was 30 (85.7%):5 (14.3%). 18 patients had exon 19 deletion (51.4%), 15 had L858R exon 21 mutation (42.9%), 1 patient (2.9%) had mutation in S7681 exon 20 along with L858R 21 and one patient (2.9%) had a T790m mutation without any other detectable EGFR mutation. CONCLUSIONS: The incidence of EGFR mutation in NSCLC is 33% from Kolkata and is typically more common in females and nonsmokers.
Keywords: Epidermal growth factor receptor by amplification refractory mutation system polymerase chain reaction, epidermal growth factor receptor from cell-free DNA, epidermal growth factor receptor mutation in Kolkata, epidermal growth factor receptor mutation in non-small-cell lung cancers from Kolkata, incidence of epidermal growth factor receptor mutation in adenocarcinoma of lungs in Kolkata, epidermal growth factor receptor mutation in Kolkata smokers
|How to cite this article:|
Chatterjee K, Ray A, Chattopadhyay B. Incidence and characteristics of Epidermal Growth Factor Receptor (EGFR) mutation in non-small-cell lung cancer (Adenocarcinoma histology): A report of 106 patients from Kolkata. Indian J Cancer 2017;54:305-7
|How to cite this URL:|
Chatterjee K, Ray A, Chattopadhyay B. Incidence and characteristics of Epidermal Growth Factor Receptor (EGFR) mutation in non-small-cell lung cancer (Adenocarcinoma histology): A report of 106 patients from Kolkata. Indian J Cancer [serial online] 2017 [cited 2020 Apr 6];54:305-7. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/305/219572
| » Introduction|| |
Lung cancer is the most common cause of cancer related mortality, claiming 1.69 million lives in 2015 worldwide. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has significantly improved clinical outcomes compared to chemotherapy in non-small-cell lung cancer (NSCLC) patients with sensitizing EGFR gene mutations. Targeted EGFR-TKI in the first-line treatment of sensitizing EGFR mutations results in longer progression-free survival, improved health-related quality of life and decreased treatment-related toxicities when compared with those who received standard chemotherapy. However, the prevalence of these mutations shows geographical variations which necessitate the generation of more and more data from centers and individual oncologists from across the globe. The data compiled in this paper presents EGFR mutation data from 106 patients from Kolkata, West Bengal and discusses the characteristics of the same with regard to the patient population.
| » Subjects and Methods|| |
Patients with NSCLC, adenocarcinoma histology, whose formalin-fixed, paraffin embedded (FFPE) samples, had been tested for EGFR mutational status between March 2014 and February 2017, were considered for this study. The main testing methods used were real-time-based amplification refractory mutation system (ARMS) polymerase chain reaction (PCR), PCR and gene sequencing, and cell-free DNA (CTDNA). Clearances from the ethical committee of treating hospitals were obtained, and clinical characteristics and treatment details were collected from the patient's medical records in a de-identified manner. The analytical sensitivity of the tests allowed detection of the mutations, when the mutant clone comprised at least 1%–5% of the total genomic DNA. The data were analyzed using simple descriptive statistics methods (Microsoft Excel).
| » Results|| |
Between March 2014 and February 2017, a total of 108 patients' FFPE samples were tested. Of these two samples were deemed inadequate for reporting. Of the remaining 106 patients, 65 (61.3%) were males and 41 (38.6%) were females. Median age of the patients was 56 years (42–72). The median age of the males was 59 years (48–72), and that of the females was 52 years (42–67). 87.7% of the tests were done using the real-time ARMS-PCR, which is based upon a combination of ARMS and scorpion technology to detect mutations on a real-time platform. 9.4% of the patients underwent PCR and gene sequencing and the remaining 2.8% were tested using CT-DNA. This reflected a change in availability of tests over the period with the earlier patients undergoing PCR and gene sequencing and the more recent patients, with tissue acquisition problems, undergoing CT-DNA-based testing.
In this study, a total of 35 (33%) patients were found to be EGFR mutation positive. Among these 16 patients (16/35 [45.7%]) were male and 19 (19/35 [54.3%]) were female. 18 patients presented with exon 19 deletion (51.4%) followed by 15 patients with L858R exon 21 mutation (42.9%). One patient (2.9%) had mutation in S7681 exon 20 along with L858R 21. Interestingly, one patient (2.9%) had a T790m mutation detected upfront without any other detectable EGFR mutation. These results along with detailed demographic characterizations are summarized in [Table 1], [Table 2], [Table 3], [Table 4].
|Table 4: Demographics of epidermal growth factor receptor positive and negative patients|
Click here to view
| » Discussion|| |
EGFR activating mutations identify a subset of patients with NSCLC whose outcome is better with tyrosine kinase EGFR targeted therapies. There is a lack of data from India regarding EGFR mutation status, especially from the eastern region. This data is one of the first attempts to collate the same from Kolkata along with its correlation with phenotypical characteristics classically used for patient selection. Most of the patients (73.6%) in our study were nonsmokers, a significant proportion (54%) was females and all of the patients had adenocarcinoma histology.
In our study, 33% of the patients were found to harbor an EGFR mutation. Previous studies from India have reported incidences of 35%–51.8%. The high numbers reported in these studies, including ours, could represent effects of a phenotypically selected group with higher chances of having genotypic positivity. Worldwide, the incidence of EGFR mutations has been well characterized and has been reported to occur at the rate of 10%–15% in North Americans and Europeans, 19% in African–Americans and about 30% in East Asians. We found that 30 of the 35 patients with EGFR mutations (85.7%) were nonsmokers, while 23 of the 71 patients who were EGFR mutation negative (32.4%) had a smoking history. 54.3% of patients with EGFR mutations were female whereas 69% of EGFR-negative tumors were male. In the female subgroup, the EGFR positivity rate was 46.3% compared to 24.6% in males [Table 4].
Regarding the type of EGFR mutations detected 51.4% of the patients were noted to have deletion in exon 19, 42.9% had the L858R point mutation in exon 21 and only 1 patient had mutation in S7681 exon 20 along with L858R 21. The data for upfront T790M patient shall be presented subsequently in another communication as it represents an extremely unusual presentation of the disease. Worldwide, approximately 45%–54% of EGFR mutations are in-frame deletions in exon 19, while approximately 40% of EGFR mutations are missense mutations in L858R in exon 21 and between 4 to 9% of the mutations were reported in exon 20.
| » Conclusion|| |
The data corresponds well to national and international datasets for the incidences as well as published phenotypical correlates but as expected, suffers from the inadequacies associated with small sample sizes and retrospective data collection.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Ahn MJ, Sun JM, Lee SH, Ahn JS, Park K. EGFR TKI combination with immunotherapy in non-small cell lung cancer. Expert Opin Drug Saf 2017;16:465-9.
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al.
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46.
Ellison G, Zhu G, Moulis A, Dearden S, Speake G, McCormack R. EGFR mutation testing in lung cancer: A review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol 2013;66:79-89.
Noronha V, Prabhash K, Thavamani A, Chougule A, Purandare N, Joshi A, et al.
EGFR mutations in Indian lung cancer patients: Clinical correlation and outcome to EGFR targeted therapy. PLoS One 2013;8:e61561.
[Table 1], [Table 2], [Table 3], [Table 4]
|This article has been cited by|
||Biomarkers in Non-Small Cell Lung Cancers: Indian Consensus Guidelines for Molecular Testing
| ||Kumar Prabhash,Suresh H. Advani,Ullas Batra,Bivas Biswas,Anuradha Chougule,Mithua Ghosh,Vamshi Krishna Muddu,T. P. Sahoo,Ashok K. Vaid |
| ||Advances in Therapy. 2019; 36(4): 766 |
|[Pubmed] | [DOI]|