Distinct clinicopathologic characteristics of lung mucinous adenocarcinoma with KRAS mutation

Primary mucinous adenocarcinomas are uncommon, and their pathogenesis remains unclear. We recently reported the clinicopathologic characteristics of surgically resected mucinous adenocarcinoma, including the frequent involvement of the left and lower lung and absence of central fibrosis. The present study attempted to clarify the pathogenesis of mucinous adenocarcinoma based on KRAS mutation status. We selected 45 mucinous adenocarcinoma cases from among 2474 surgically resected primary lung adenocarcinomas. Of these, 22 had a KRAS mutation (48.9%), whereas only 7 (15.6%) had an epidermal growth factor receptor mutation, and 2 cases had both mutations. The mucinous adenocarcinomas with KRAS mutations were located in the lower lung lobe significantly more often (P <.05) than were tumors without KRAS mutation. The mucinous adenocarcinoma cases with KRAS mutations also had a significantly lower frequency of nuclear atypia (P <.05). We compared the degree of immunostaining for matrix metalloproteinase-7 (MMP-7), laminin-5, and geminin in the mucinous adenocarcinoma with and without KRAS mutation. The proportion of geminin-positive cells was lower among the cases with a mutation than among those without (0.7% versus 2.1%; P <.05). No significant differences in the extent of staining of the other markers were observed between the groups. The current study clearly demonstrated that mucinous adenocarcinomas with KRAS mutations have clinicopathologic characteristics different from those of mucinous adenocarcinoma without such mutations.