Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients

Background: To evaluate differences in the clinical characteristics and molecular pathology of lung adenocarcinoma subtypes as defined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international histological classification.

Methods: We retrospectively reviewed 269 patients with initial primary lung adenocarcinoma who had undergone complete resection at our department from August 2013 to December 2014, focusing on the new histologic subtype classification, clinical characteristics, and molecular pathology.

Results: All specimens were invasive adenocarcinoma, and were lepidic (13.0%), papillary (19.7%), acinar (51.7%), solid (8.6%), micropapillary (1.1%) or mucinous predominant (5.9%). Epidermal growth factor receptor (EGFR) mutations were detected in 132 cases (60.3%). Female patients and non-smokers had higher EGFR mutation rates (P = 0.022 and 0.026, respectively). The lepidic, papillary, acinar, solid, micropapillary, and mucinous predominant patterns had EGFR mutation rates of 70.6%, 64.8%, 72.5%, 33.3%, 100%, and 5.9%, respectively. The exon mutation distribution differed according to serum carcinoembryonic antigen (CEA) levels (P = 0.018). v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected in 20 cases (9.2%), and were frequently found in the mucinous and solid predominant subtypes. The serum CEA levels differed among the subtypes.

Conclusions: In China, there are significant differences between lung adenocarcinoma histologic subtypes. The presence of well-differentiated components in lung adenocarcinoma indicates higher EGFR mutation rates; the presence of solid or mucinous components indicates higher KRAS mutation rates. Serum CEA levels are associated with histologic subtype and EGFR exon mutations.