Pulmonary invasive mucinous adenocarcinoma and mixed invasive mucinous/nonmucinous adenocarcinoma—a clinicopathological and molecular genetic study with survival analysis

Jennifer M. Boland, Joseph Maleszewski, Jason A. Wampfler, Jesse S. Voss, Benjamin R. Kipp, Ping Yang, Eunhee S. Yi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Invasive mucinous adenocarcinoma is a variant of lung adenocarcinoma, which may be mixed with nonmucinous adenocarcinoma. KRAS mutations are common, but other clinical and genetic features are not clearly established. Lung adenocarcinomas (n = 760) with ≥5 years of follow-up comprised 3 nonoverlapping cohorts for survival analysis. Mucinous tumors were evaluated with Ion AmpliSeq Cancer Hotspot Panel v2. Cases without detected mutations were tested for ALK and ROS1 and by OncoScan array. Fifty-seven invasive mucinous adenocarcinomas and 54 mixed mucinous/nonmucinous adenocarcinomas were identified. Mucinous tumors constituted 27 of 218 nonselected 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/nonmucinous), 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/nonmucinous. Four of 6 cases without hotspot mutations showed complex copy number/structural abnormalities. Pulmonary invasive mucinous adenocarcinomas and mixed nonmucinous/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 that for nonmucinous tumors in a nonselected cohort, although worse survival was seen in a cohort of smokers enriched for lepidic growth.

Original languageEnglish (US)
Pages (from-to)8-19
Number of pages12
JournalHuman Pathology
Volume71
DOIs
StatePublished - Jan 1 2018

Fingerprint

Mucinous Adenocarcinoma
Survival Analysis
Molecular Biology
Lung
Mutation
Neoplasms
Survival
Growth
Disease-Free Survival
Adenocarcinoma
Cohort Studies
Ions

Keywords

  • KRAS
  • Mucinous adenocarcinoma
  • Mutations
  • Never smoker
  • STK11
  • Survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pulmonary invasive mucinous adenocarcinoma and mixed invasive mucinous/nonmucinous adenocarcinoma—a clinicopathological and molecular genetic study with survival analysis. / Boland, Jennifer M.; Maleszewski, Joseph; Wampfler, Jason A.; Voss, Jesse S.; Kipp, Benjamin R.; Yang, Ping; Yi, Eunhee S.

In: Human Pathology, Vol. 71, 01.01.2018, p. 8-19.

Research output: Contribution to journalArticle

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abstract = "Invasive mucinous adenocarcinoma is a variant of lung adenocarcinoma, which may be mixed with nonmucinous adenocarcinoma. KRAS mutations are common, but other clinical and genetic features are not clearly established. Lung adenocarcinomas (n = 760) with ≥5 years of follow-up comprised 3 nonoverlapping cohorts for survival analysis. Mucinous tumors were evaluated with Ion AmpliSeq Cancer Hotspot Panel v2. Cases without detected mutations were tested for ALK and ROS1 and by OncoScan array. Fifty-seven invasive mucinous adenocarcinomas and 54 mixed mucinous/nonmucinous adenocarcinomas were identified. Mucinous tumors constituted 27 of 218 nonselected 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/nonmucinous), 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/nonmucinous. Four of 6 cases without hotspot mutations showed complex copy number/structural abnormalities. Pulmonary invasive mucinous adenocarcinomas and mixed nonmucinous/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 that for nonmucinous tumors in a nonselected cohort, although worse survival was seen in a cohort of smokers enriched for lepidic growth.",
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