DOI: 10.4103/ijpm.ijpm_193_25 ISSN: 0377-4929

Spectrum of common and uncommon compound epidermal growth factor receptor mutations in non-small cell lung carcinoma: An institutional experience from tertiary care centers from Eastern India

Mukund N. Sable, Swetasmita Mishra, Susama Patra, Pritinanda Mishra, Prashanta R. Mahapatra, Saroj Das Majumdar, Saurav K. Mishra
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ABSTRACT

Background:

Non-small cell lung cancer (NSCLC) constitutes about 85% of lung cancer cases. Epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR -TKIs) have improved survival rates in patients with EGFR -sensitizing mutations. Compound mutations in the EGFR gene are infrequent in NSCLC, with an incidence of usually <1%. The objective of this investigation is to identify compound EGFR mutations in NSCLC and to elucidate their associations with clinic-pathological profiles.

Materials and Methods:

All histologically and immunohistochemically proven cases of NSCLC with compound EGFR mutation from the year 2017–2024 were studied. Clinicopathological details like age, sex, histopathological characteristics, and follow-up were recorded.

Results:

Out of 642 NSCLC cases, 248 (38.62%) were EGFR mutation-positive. The most common mutations were exon 19 deletions (152 cases, 58%) and exon 21 mutations (79 cases, 30.15%). Compound mutations were found in 16/642 cases (2.49%), of which 15 had dual mutations and one had a triple mutation. The common + common mutation ( del19-L858R) was identified in 2/16 cases. Common + rare mutations were the most frequent compound mutations [ del19-T790M (6/16), T790M-L858R (4/16), and S768I-L858R (1/16)], while rare + rare mutations G 719X-S768I were seen in 2/16 cases. Only one case exhibited triple compound mutation ( del19 + G719X + S768I ). All patients with compound mutations had adenocarcinoma of lung origin. Only one patient with T790M-L858R mutations was ROS1 -positive. The median survival period appeared shorter in common + rare mutations compared to rare + rare mutations.

Conclusions:

Nearly 7% of EGFR mutations in NSCLC patients were compound mutations, which is comparable to previous reports. The presence of multiple mutations, particularly those involving T790M , may be associated with potential resistance to first-line EGFR -TKIs. We describe a triple mutation involving del19 + G719X + S768I , which represents an uncommon scenario.

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