Pulmonary Invasive Mucinous Adenocarcinoma and Mixed Invasive Mucinous/Non-Mucinous Adenocarcinoma- A Clinicopathological and Molecular Genetic Study with Survival Analysis

Publication date: Available online 17 August 2017
Source:Human Pathology
Author(s): Jennifer M. Boland, Joseph J. Maleszewski, Jason A. Wampfler, Jesse S. Voss, Benjamin R. Kipp, Ping Yang, Eunhee S. Yi
Invasive mucinous adenocarcinoma is a variant of lung adenocarcinoma, which may be mixed with non-mucinous adenocarcinoma. KRAS mutations are common, but other clinical and genetic features are not clearly established. Lung adenocarcinomas (n=760) with ≥5years follow-up comprised 3 non-overlapping cohorts for survival analysis. Mucinous tumors were evaluated with Ion AmpliSeq™ Cancer Hotspot Panel v2. Cases without detected mutations were tested for ALK, ROS1, and by OncoScan array. Fifty-seven invasive mucinous adenocarcinomas and 54 mixed mucinous/non-mucinous adenocarcinomas were identified. Mucinous tumors constituted 27 of 218 non-selected patients (12.4%), 23 of 268 never smokers (8.6%), and 61 of 274 in a smokers cohort enriched for lepidic growth (22.3%). In the lepidic-enriched smokers, patients with mucinous tumors experienced worse overall survival (P=.006) and progression-free survival (P=.024), which persisted on multivariable analysis. No survival differences were observed in the other cohorts. KRAS mutations were common (76% of invasive mucinous adenocarcinomas, 68% of mixed mucinous/non-mucinous), and 38% of KRAS mutations occurred with other mutations, especially STK11. Six cases had potentially targetable mutations (3 ALK, 2 EGFR, 1 BRAF V600E). All ALK rearranged tumors were mixed mucinous/non-mucinous. Four of 6 cases without hotspot mutations showed complex copy number/structural abnormalities. Pulmonary invasive mucinous adenocarcinomas and mixed non-mucinous/mucinous adenocarcinomas are clinically and genetically similar, except for a higher rate of ALK rearrangement in mixed tumors. Survival for mucinous tumors is similar to non-mucinous tumors in a non-selected cohort, although worse survival was seen in a cohort of smokers enriched for lepidic growth.



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