title: Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma.
abstract: BACKGROUND
  As the comprehensive genomic analysis of small cell lung cancer (SCLC) progresses, novel treatments for this disease need to be explored. With attention to the direct connection between the receptor tyrosine kinases (RTKs) of tumor cells and the pharmacological effects of specific inhibitors, we systematically assessed the RTK expressions of high-grade neuroendocrine carcinomas of the lung [HGNECs, including SCLC and large cell neuroendocrine carcinoma (LCNEC)].
  
  
  METHODS
  Fifty-one LCNEC and 61 SCLC patients who underwent surgical resection were enrolled in this research. As a control group, 202 patients with adenocarcinomas (ADCs) and 122 patients with squamous cell carcinomas (SQCCs) were also analyzed. All the tumors were stained with antibodies for 10 RTKs: c-Kit, EGFR, IGF1R, KDR, ERBB2, FGFR1, c-Met, ALK, RET, and ROS1.
  
  
  RESULTS
  The LCNEC and SCLC patients exhibited similar clinicopathological characteristics. The IHC scores for each RTK were almost equivalent between the LCNEC and SCLC groups, but they were significantly different from those of the ADC or SQCC groups. In particular, c-Kit was the only RTK that was remarkably expressed in both LCNECs and SCLCs. On the other hand, about 20 % of the HGNEC tumors exhibited strongly positive RTK expression, and this rate was similar to those for the ADC and SQCC tumors. Intriguingly, strongly positive RTKs were almost mutually exclusive in individual tumors.
  
  
  CONCLUSIONS
  Compared with ADC or SQCC, LCNEC and SCLC had similar expression profiles for the major RTKs. The exclusive c-Kit positivity observed among HGNECs suggests that c-Kit might be a distinctive RTK in HGNEC.
authors.affiliation: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.|Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.|Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan. sumemura@east.ncc.go.jp.|Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. sumemura@east.ncc.go.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.affiliation: Pathology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.affiliation: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.|Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Aokage
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hishida
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.|Division of Thoracic Oncology, National Cancer Center Hospital, Kashiwa, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.affiliation: Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tsuchihara
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit
keywords: High-grade neuroendocrine carcinoma; Immunohistochemical staining; Lung cancer; Receptor tyrosine kinase