Mucinous lung adenocarcinoma, particularly referring to EGFR-mutated mucinous adenocarcinoma.

Abstract

The current 2015 World Health Organization (WHO) classification of lung tumors does not adequately categorize mucinous lung adenocarcinoma. Thus far, only two variants of mucinous adenocarcinoma have been studied: invasive mucinous adenocarcinoma and colloid adenocarcinoma. Moreover, common types of invasive adenocarcinoma when they produce mucin are yet to be elucidated, particularly epidermal growth factor receptor (EGFR)-mutated mucinous adenocarcinoma. In this study, we extracted mucinous adenocarcinoma of both the common types and the two variants. Further, we immunohistochemically and molecular-biologically examined their clinicopathological characteristics, mutation patterns, and expressions of thyroid transcription factor-1 (TTF-1), hepatocyte nuclear factor-4 alpha (HNF-4a) and mucins, particularly referring to EGFR-mutated adenocarcinoma. Among 1159 surgically resected invasive adenocarcinomas, 189 mucinous adenocarcinomas (16%) were identified. Among these, 20%, 34% and 9.5% were EGFR mutated, KRAS mutated and ALK rearranged, respectively. Compared with EGFR-mutated nonmucinous adenocarcinoma, EGFR-mutated mucinous adenocarcinoma had no female predominance, lower grades of histological differentiation and lower TTF-1 and higher HNF-4a expressions. Moreover, for the first time, we indicated that mucin production was an independent prognostic factor for EGFR-mutated adenocarcinomas and the mucin-staining pattern of negative MUC5AC and positive MUC5B was characteristic in these adenocarcinomas. We suggest that EGFR-mutated mucinous adenocarcinoma has a different tumorigenic pathway than nonmucinous EGFR-mutated adenocarcinoma.