Abstract
Background: Epidermal growth factor receptor (EGFR) mutations have been known to be associated with adenocarcinoma, women, non- smokers and East-Asian ethnicity. This study was aimed to characterize the frequency of EGFR mutations and their association with histologic subtypes in primary lung adenocarcinoma in an Indian cohort. Methods: Two seventy-four cases were categorized using 2015 WHO classification of lung tumors. The frequency of each histologic subtype and cell type was correlated with EGFR exon sequences in a subset of 120 cases using polymerase chain reaction (PCR) gene sequencing. Results: The predominant biopsy categories in 274 cases were acinar 167(61%), solid 63(23%), mucinous 19(7%), lepidic 11(4%) and others 14(5%). EGFR mutations were detected in 49/120 (40.8%) including 3/5(60%) lepidic, 4/9(44.4%) papillary, 29/68(42.7%) acinar, 10/24(41.7%) solid and 1/13(7.7%) mucinous subtypes and were significantly associated with the cuboidal cell type (p=0.01). These mutations were common in women and non-smokers, although not statistically significant. Exon 19 mutations predominated in 36/49(73.4%). The majority, 213/263 (81%), were thyroid transcription factor 1(TTF-1) positive. The polygonal cell type and the solid subtype were frequent amongst stage IV tumors and smokers. Conclusions : EGFR mutations were most frequently seen with the lepidic and papillary subtypes, not associated with the mucinous subtype, more common in women and non-smokers and significantly associated with the cuboidal cell type. DOI: 10.21276/APALM.1372
Highlights
Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers
NSCLC is classified into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma
The New International classification (IASLC/ATS/ERS)[3,4] and 2015 World Health Organization (WHO) classification[5]”defined the adenocarcinoma in situ(AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic adenocarcinoma, replaced the ‘mixed subtype category’ in 2004 WHO classification[6] with the predominant subtype, included the micropapillary subtype and replaced the term “mucinous bronchioloalveolar carcinoma (BAC)” with invasive mucinous adenocarcinoma
Summary
Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. NSCLC is classified into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. In India, squamous cell carcinoma has been the most common histological type of NSCLC with a growing predominance of adenocarcinoma[1]. Lung adenocarcinomas are well known to display inter and intra-tumoral heterogeneity with profound implications for exact histological classification by pathologistsaccounting for more deaths than breast, prostate and colon cancer combined.[2] While treatment decisions are determined primarily by stage, therapeutically non small cell lung cancer Epidermal growth factor receptor (EGFR) mutations have been known to be associated with adenocarcinoma, women, non- smokers and East-Asian ethnicity. This study was aimed to characterize the frequency of EGFR mutations and their association with histologic subtypes in primary lung adenocarcinoma in an Indian cohort
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