EGFR and KRAS Mutations in Lung Parenchyma of Subjects With EGFR/KRAS Wild-Type Lung Adenocarcinoma

• Published in: Pathology oncology research Vol. 27; p. 598292
• Main Authors: Chalela, Roberto, González-García, Jose Gregorio, Khilzi, Karys, Curull, Víctor, Sánchez-Font, Albert, Longarón, Raquel, Rodrigo-Calvo, María Teresa, Martín-Ontiyuelo, Clara, Gea, Joaquim, Bellosillo, Beatríz
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media SA 24.03.2021; Frontiers Media S.A
• Subjects: Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - pathology; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Cancer; Case-Control Studies; ErbB Receptors - genetics; Experiments; Female; Follow-Up Studies; Humans; Hypotheses; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical prognosis; Middle Aged; Mutation; Parenchymal Tissue - metabolism; Parenchymal Tissue - pathology; Prognosis; Proto-Oncogene Proteins p21(ras) - genetics; Society Journal Archive; KRAS; Prognosis; EGFR–epidermal growth factor receptor; adenocacinoma lung; driver mutation
• ISSN: 1532-2807; 1219-4956; 1532-2807
• DOI: 10.3389/pore.2021.598292

The acquisition of driver mutations in non-tumoral cells appears to be very important during the carcinogenesis of adenocarcinoma (ADC). Recent studies suggest that cancer-related mutations may not necessarily be present only in malignant cells, but also in histologically “healthy cells”. Objective: to demonstrate the presence of EGFR or KRAS mutations in non-tumoral lung cells in subjects with ADC and negative mutational status. Results: mutations in EGFR or KRAS oncogenes were identified in the normal lung in 9.7% of the subjects. Exon 21 substitution L858R in EGFR was detected in two cases while the exon 19 deletion E746-A750 in the EGFR , the G12C and G12D substitutions in the KRAS were detected once. One patient presented three different mutations in the normal lung parenchyma ( EGFR _L858R, KRAS _G12C and KRAS _G12D). The negative-mutation status of the tumor and the mutations detected in the “normal lung” were confirmed using highly sensitive and specific TaqMan PCR (CAST-PCR). No differences were found in terms of progression, progression-free survival or overall survival during the 18 months follow-up. Conclusions: These results confirm the presence of driver mutations in the histologically normal lung parenchyma cells in the absence of mutations coexisting with the primary tumor.