Comparison of clinical features, molecular alterations, and prognosis in morphological subgroups of lung invasive mucinous adenocarcinoma

PURPOSE We performed this analysis to distinguish the differences in two subtypes of lung invasive mucinous adenocarcinoma (IMA) with different kinds of morphological performances, in clinicopathological and molecular features, as well as prognosis. METHODS On the basis of morphological performance, we divided lung IMAs into two subgroups, mucus-in-cell adenocarcinoma (MICA) and mucus-out-of-cell adenocarcinoma (MOCA). We investigated differences in clinicopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and a spectrum of well-identified driver-gene mutations, including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET, between the two subgroups. RESULTS Of 1,699 lung adenocarcinomas, 148 were identified as IMAs (97 MICAs and 51 MOCAs). The MICA patient group had significantly better RFS than did the MOCA group (39.4 months versus 33.0 months, respectively, log rank P=0.020) and significantly better OS (54.2 months versus 45.1 months, log rank P=0.034). There were no differences in RFS and OS between those with IMAs and those with mucus-negative adenocarcinomas. The frequency of the EGFR gene mutation was significantly higher in MOCAs than in MICAs (P<0.001). In contrast, the KRAS gene had a significantly higher mutational frequency in MICAs (P=0.01). MOCAs also had a significantly higher incidence of lymph-node metastasis (P<0.05). CONCLUSION To our knowledge, this study represents the first comparison of clinical features, molecular alterations, and prognosis in morphological subgroups of lung IMAs. Clinical and pathological features in conjunction with molecular data indicate that IMA should be divided into different subgroups.