Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: Invasive mucinous pattern and extracellular mucin are associated with KRAS mutation Journal Article


Authors: Kadota, K.; Yeh, Y. C.; D'Angelo, S. P.; Moreira, A. L.; Kuk, D.; Sima, C. S.; Riely, G. J.; Arcila, M. E.; Kris, M. G.; Rusch, V. W.; Adusumilli, P. S.; Travis, W. D.
Article Title: Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: Invasive mucinous pattern and extracellular mucin are associated with KRAS mutation
Abstract: Multiple reports indicate that epidermal growth factor receptor (EGFR) mutations are associated with lepidic-pattern lung adenocarcinoma and that KRAS mutations are associated with invasive mucinous adenocarcinoma. We sought to investigate the association between EGFR and KRAS mutations and specific morphologic characteristics, such as predominant histologic subtype and mucinous features. Clinical data for 864 patients with resected lung adenocarcinoma that underwent molecular testing for EGFR and KRAS mutations were collected. Histologic subtyping was performed according to the IASLC/ATS/ERS lung adenocarcinoma classification, with attention given to signet-ring cell feature and extracellular mucin. EGFR mutations were detected using a polymerase chain reaction-based sizing assay, KRAS mutations were detected using Sanger sequencing, and ALK expression was detected using immunohistochemistry. Invasive mucinous adenocarcinoma was associated with KRAS mutation (P<0.001). Among invasive mucinous adenocarcinomas with KRAS mutation, a pure mucinous pattern was more common than a mixed mucinous/nonmucinous pattern (P=0.002). Invasive mucinous adenocarcinoma was associated with KRAS transition mutations (G→A) but not transversion mutations (G→T or G→C) compared with nonmucinous tumors (P=0.009). The lepidic-predominant group was associated with EGFR mutation compared with nonlepidic-predominant tumors (P=0.011). Extracellular mucin was associated with KRAS mutation (P<0.001), whereas signet-ring cell feature was not associated with EGFR or KRAS mutation (P=0.517). ALK expression was associated with signet-ring cell feature (P=0.001) but not with extracellular mucin (P=0.089). Our study shows that histologic patterns of mucin in lung adenocarcinoma - including invasive mucinous adenocarcinoma and extracellular mucin - are associated with KRAS mutation. © 2014 by Lippincott Williams & Wilkins.
Keywords: mutation; adenocarcinoma; lung; mucin; subtype
Journal Title: American Journal of Surgical Pathology
Volume: 38
Issue: 8
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2014-08-01
Start Page: 1118
End Page: 1127
Language: English
DOI: 10.1097/pas.0000000000000246
PROVIDER: scopus
PUBMED: 25029118
PMCID: PMC4666292
DOI/URL:
Notes: Export Date: 1 August 2014 -- CODEN: AJSPD -- Source: Scopus
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MSK Authors
  1. Camelia S Sima
    212 Sima
  2. Valerie W Rusch
    864 Rusch
  3. Andre L Moreira
    176 Moreira
  4. William D Travis
    743 Travis
  5. Gregory J Riely
    599 Riely
  6. Sandra Pierina D'Angelo
    252 D'Angelo
  7. Kyuichi Kadota
    85 Kadota
  8. Maria Eugenia Arcila
    657 Arcila
  9. Deborah Kuk
    87 Kuk
  10. Mark Kris
    869 Kris
  11. Yi-Chen Yeh
    10 Yeh