P02.25 Coexistence of Invasive Adenocarcinoma, Minimally Invasive Adenocarcinoma and Atypical Adenomatous Hyperplasia: A Case Report

Abstract

Multiple small nodular lung cancer (MSLC) refers to multiple tumor nodules on the same or different lobes of the lungs. These nodules are affected by the same germline characteristics and environmental exposure factors that occur simultaneously in one individual. Invasive adenocarcinoma (inv ADC), minimally invasive adenocarcinoma (MIA) and atypical adenomatous hyperplasia (AAH) are regarded as the “three-steps” in the evolution of lung adenocarcinoma. A fifty-year-old Asian female patient without a history of smoking was hospitalized due to three ground-glass nodules (GGNs) in the right upper lobe of the lung, which were detected in March 2017. Three nodules revealed by chest CT were each pathologically diagnosed as ADC, MIA and AAH. To further confirm the correlations and differences among these types, we performed whole-exome sequencing on the three lesions followed by a comparative analysis at the genetic level to determine the major genes that may play an important role in the progression of these “three-steps” in lung adenocarcinoma. The TMB of the three lesions was relatively low, especially in AAH.(Fig 2C) The three lesions were found to share a common gene (BAGE2).(Fig 2B) We found that MAP3K14, MAP2K1, and EGFR, which are three major genes of the EGFR-MAPK pathway, may play an important role in AAH, MIA and inv ADC, respectively.(Fig 2D) The C>T alteration was the primary change observed in the three nodules of the patient. C>A was increased in the ADC nodule and decreased in the MIA nodule, but was rare in AAH.(Fig 2E, F) We found that MAP3K14, MAP2K1, and EGFR were three dominant factors that exist as part of “three-steps” and that might act as new specific targets for the treatment of this disease type. However, the relationship among MAP2K1, MAP3K14 and EGFR still requires more verification in more samples.