EGFR and KRAS mutations in the non-tumoral lung. Prognosis in patients with adenocarcinoma

Chalela Rengifo, Roberto José, 1985-; Bellosillo Paricio, Beatriz; Curull Serrano, Víctor; Longarón Rozalen, Raquel; Pascual Guàrdia, Sergi, 1979-; Badenes Bonet, Diana, 1987-; Arriola Aperribay, Edurne; Sánchez-Font, Albert; Pijuan Andujar, Lara; Gea Guiral, Joaquim

doi:http://dx.doi.org/10.3390/jcm8040529

EGFR and KRAS mutations in the non-tumoral lung. Prognosis in patients with adenocarcinoma

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Chalela R, Bellosillo B, Curull V, Longarón R, Pascual-Guardia S, Badenes-Bonet D et al. EGFR and KRAS mutations in the non-tumoral lung. Prognosis in patients with adenocarcinoma. J Clin Med. 2019 Apr 17;8(4):529. DOI: 10.3390/jcm8040529

Abstract

Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung. Objective: To analyze whether the most prevalent mutations observed in ADC can also be observed in the non-neoplastic lung tissue, as well as the short-term prognosis implications of this finding. Methods: Non-tumoral lung parenchyma specimens obtained during surgery from 47 patients with EGFR and/or KRAS abnormalities in their ADC tumors underwent similar genomic testing. Short-term outcomes were also recorded. Results: The same mutations were present in the tumor and the histologically normal tissue in 21.3% of patients (SM group). Although local recurrences were similar in both groups, distant metastases were more frequent in the former (60 vs. 5.4%, p < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, p < 0.001) and disease-free survival (8.5 vs. 11.2 months, p < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, p < 0.01]. Similar results were observed when adjusting for potential confounding variables. Conclusions: These results confirm that genetic changes are present in the apparently normal lung in many ADC patients, and this finding has prognostic implications.