title: Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma.
abstract: OBJECTIVE
  Pulmonary adenosquamous carcinoma (ASC) is more aggressive than adenocarcinoma (AC) and squamous cell carcinoma (SCC). The genetic features and biomarkers of ASC are not well known. Here, we attempted to identify potential therapeutic markers for ASC.
  
  
  RESULTS
  Surgically resected ASC samples from 65 patients were analysed. We examined the expression of β III-tubulin, thymidylate synthase, breast cancer susceptibility gene 1 and ribonucleotide reductase M1 (RRM1); identified mutations in epidermal growth factor receptor (EGFR), KRAS, BRAF and HER2; and detected ALK, ROS1 and RET rearrangements. Gene amplification and expression of EGFR, human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor-1 and MET were also examined. β III-Tubulin showed the highest expression (P = 0.002), and its expression was more frequent in the AC than in the SCC component (P = 0.013). RRM1 expression was more frequent in the SCC component (P = 0.046). EGFR and KRAS mutations were detected in both components (21.5 and 10.9%, respectively). ALK and ROS1 rearrangements and MET amplification were detected in both components in one (1.5%) case.
  
  
  CONCLUSIONS
  In ASC, drug response-specific gene alterations could occur in both AC and SCC components, suggesting that patients with confirmed or suspected ASC should undergo further testing for driver gene analyses.
authors.affiliation: Division of Pathology, National Cancer Centre Hospital, Tokyo, Japan.|Department of Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.|Division of Thoracic Surgery, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Division of Genome Biology, National Cancer Centre Research Institute, Tokyo, Japan.
authors.forename: Kouya
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Department of Clinical Medicine (Biostatistics), School of Pharmacy, Kitasato University, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takahashi
authors.affiliation: Division of Pathology, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Department of Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Division of Thoracic Surgery, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.affiliation: Department of Clinical Medicine (Biostatistics), School of Pharmacy, Kitasato University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Division of Pathology, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.affiliation: Division of Pathology, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor
keywords: adenosquamous carcinoma; biomarker expression; druggable gene alterations