| Summary: | 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 <i>EGFR</i> and/or <i>KRAS</i> 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%, <i>p</i> < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, <i>p</i> < 0.001) and disease-free survival (8.5 vs. 11.2 months, <i>p</i> < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, <i>p</i> < 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.
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