Abstract
Numerous studies have been published on single aspects of pulmonary adenocarcinoma (ADC). To comprehensively link clinically relevant ADC characteristics, we evaluated established morphologic, diagnostic, and predictive biomarkers in 425 resected ADC.
Morphology was reclassified. CK7, TTF1, napsin A, thymidylate synthase (TS), and ERCC1 expression, ALK rearrangements as well as EGFR, KRAS and BRAF mutations were analysed. All characteristics were correlated with clinical and survival parameters.
Morphologic ADC subtypes were significantly associated with smoking history and distinct patterns of diagnostic biomarkers. KRAS mutations were prevalent in male smokers while EGFR mutations were associated with female sex, non-smoking and lepidic as well as micropapillary growth patterns. TTF1 expression (HR for OS=0.61, p=0.021) and BRAF mutations (HR for DFS=2.0, p=.046) were found as morphology- and stage-independent predictors of survival in multivariate analysis. Adjuvant radio-/chemotherapy in some instances strongly impacted on the prognostic effect of both diagnostic and predictive biomarkers.
Our data draw a comprehensive picture of the prevalence and interplay of yet established histological and molecular ADC characteristics. This data will help to develop time and cost effective diagnostic and treatment algorithms for ADC.
- ERS