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EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma

Respiratory Medicine Department, Hospital del Mar, 08003 Barcelona, Spain
IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
School of Health & Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
CIBER de Enfermedades Respiratorias (CibeRes), Instituto de Salud Carlos III, 28029 Madrid, Spain
Department of Pathology, Hospital del Mar, 08003 Barcelona, Spain
Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
Department of Oncology, Hospital del Mar, 08003 Barcelona, Spain
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(4), 529;
Received: 7 March 2019 / Revised: 5 April 2019 / Accepted: 14 April 2019 / Published: 17 April 2019
(This article belongs to the Section Pulmonology)
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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. View Full-Text
Keywords: Adenocarcinoma; Mutations; EGFR; KRAS; Prognosis Adenocarcinoma; Mutations; EGFR; KRAS; Prognosis

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Chalela, R.; Bellosillo, B.; Curull, V.; Longarón, R.; Pascual-Guardia, S.; Badenes-Bonet, D.; Arriola, E.; Sánchez-Font, A.; Pijuan, L.; Gea, J. EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma. J. Clin. Med. 2019, 8, 529.

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