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

Chalela R1,2,3,4, Bellosillo B5,6,7, Curull V8,9,10,11, Longarón R12, Pascual-Guardia S13,14,15,16, Badenes-Bonet D17,18,19, Arriola E20,21, Sánchez-Font A22,23,24, Pijuan L25, Gea J26,27,28,29.

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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.