Pulmonary adenocarcinoma with mucin production and possible subtyping based on driver mutations and transcription factors

[Abstract] The current WHO classification of lung cancer cannot appropriately characterize adenocarcinoma with mucin production. No suitable entity or typical adenocarcinoma with mucin has been established, and only two variants exist : invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma. To obtain basic data toward appropriate classification, we sought to study the characterization of adenocarcinoma with mucin production based on criteria that account for both cytoplasmic and glandular mucin, as well as a mucin lake. EGFR and KRAS mutations and protein expression of TTF-1 and HNF4a were examined in 90 cases extracted from 748 consecutive adenocarcinomas. Among the 90 tumors, 14 were IMAs, and 76 were not. The non-IMA group had fewer mucin lakes (74%), more moderately/poorly differentiated tumors (57%), more EGFR (26%) mutations and fewer KRAS (34%) mutations than the IMA group. Interestingly, the tumors were divided into the three subtypes, TTF-1-positive, HNF4a-positive and double-negative, almost exclusively. In conclusion, with the use of wider criteria for mucin production, as well as driver mutations and transcription factor expression, we may be able to establish criteria for adenocarcinomas with mucin, which may lead to the more appropriate classification of mucinous adenocarcinoma in the future.