Abstract 4173: MicroRNA expression of non-terminal respiratory unit type lung adenocarcinoma.

Abstract

Abstract Background: Lung adenocarcinomas can be classified into two major subtypes, terminal respiratory unit (TRU) type and non-TRU type. We previously reported that non-TRU type adenocarcinoma has unique clinical and morphological features compared with TRU type adenocarcinoma. In brief, among 36 cases of non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma. Objectives: We investigated whether microRNA (miRNA) expression profiles can differentiate between non-TRU type and TRU type lung adenocarcinoma. Methods: MiRNA expression in lung adenocarcinoma with non-TRU and TRU type was analyzed by microarray analysis with 1205 human and 144 human viral miRNAs. Results: Eight pairs of lung adenocarcinomas and corresponding noncancerous lung tissues (4 for non-TRU type and 4 for TRU type) were analyzed by microarray analysis. Initially, 44 miRNAs showed statistical differences in expression between lung cancer tissues and corresponding noncancerous tissues. Comparison analyses between non-TRU type and TRU type revealed 30 miRNAs with statistically different expression. Particularly, hsa-mir-494 and ebv-mir-BART19 were upregulated with more than 5-fold difference as compared with TRU type adenocarcinoma. Similarly, hsa-mir-551b was downregulated at more than 5-fold as compared with TRU type adenocarcinoma. Only 2 miRNAs (hsa-mir-1 and hsa-mir-133b) were shared in both non-TRU and TRU type of adenocarcinoma. Conclusion: We demonstrated that non-TRU type adenocarcinoma showed different miRNAs expression patterns compared with TRU type adenocarcinoma, suggesting different carcinogenic pathways for these tumors. Further studies are required for validation the results from microarray analysis. Citation Format: Mi Hyun Kim, Min Ki Lee, Dong Hoon Shin, Chang Hun Lee. MicroRNA expression of non-terminal respiratory unit type lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4173. doi:10.1158/1538-7445.AM2013-4173