Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma

Yuki Matsumura, Shigeki Umemura, Genichiro Ishii, Koji Tsuta, Shingo Matsumoto, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Yuichiro Ohe, Hiroyuki Suzuki, Atsushi Ochiai, Koichi Goto, Kanji Nagai, Katsuya Tsuchihara

Research output: Contribution to journalArticle

19 Citations (Scopus)

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)]. Patients and 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.

Original languageEnglish
Pages (from-to)2159-2170
Number of pages12
JournalJournal of Cancer Research and Clinical Oncology
Volume141
Issue number12
DOIs
Publication statusPublished - 2015 May 20
Externally publishedYes

Fingerprint

Neuroendocrine Carcinoma
Receptor Protein-Tyrosine Kinases
Squamous Cell Carcinoma
Adenocarcinoma
Small Cell Lung Carcinoma
Large Cell Carcinoma
Lung
Neoplasms
Pharmacology
Control Groups

Keywords

  • High-grade neuroendocrine carcinoma
  • Immunohistochemical staining
  • Lung cancer
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung : a comparative analysis with adenocarcinoma and squamous cell carcinoma. / Matsumura, Yuki; Umemura, Shigeki; Ishii, Genichiro; Tsuta, Koji; Matsumoto, Shingo; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Ohe, Yuichiro; Suzuki, Hiroyuki; Ochiai, Atsushi; Goto, Koichi; Nagai, Kanji; Tsuchihara, Katsuya.

In: Journal of Cancer Research and Clinical Oncology, Vol. 141, No. 12, 20.05.2015, p. 2159-2170.

Research output: Contribution to journalArticle

Matsumura, Y, Umemura, S, Ishii, G, Tsuta, K, Matsumoto, S, Aokage, K, Hishida, T, Yoshida, J, Ohe, Y, Suzuki, H, Ochiai, A, Goto, K, Nagai, K & Tsuchihara, K 2015, 'Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma', Journal of Cancer Research and Clinical Oncology, vol. 141, no. 12, pp. 2159-2170. https://doi.org/10.1007/s00432-015-1989-z
Matsumura, Yuki ; Umemura, Shigeki ; Ishii, Genichiro ; Tsuta, Koji ; Matsumoto, Shingo ; Aokage, Keiju ; Hishida, Tomoyuki ; Yoshida, Junji ; Ohe, Yuichiro ; Suzuki, Hiroyuki ; Ochiai, Atsushi ; Goto, Koichi ; Nagai, Kanji ; Tsuchihara, Katsuya. / Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung : a comparative analysis with adenocarcinoma and squamous cell carcinoma. In: Journal of Cancer Research and Clinical Oncology. 2015 ; Vol. 141, No. 12. pp. 2159-2170.
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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)]. Patients and 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.",
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T1 - Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung

T2 - a comparative analysis with adenocarcinoma and squamous cell carcinoma

AU - Matsumura, Yuki

AU - Umemura, Shigeki

AU - Ishii, Genichiro

AU - Tsuta, Koji

AU - Matsumoto, Shingo

AU - Aokage, Keiju

AU - Hishida, Tomoyuki

AU - Yoshida, Junji

AU - Ohe, Yuichiro

AU - Suzuki, Hiroyuki

AU - Ochiai, Atsushi

AU - Goto, Koichi

AU - Nagai, Kanji

AU - Tsuchihara, Katsuya

PY - 2015/5/20

Y1 - 2015/5/20

N2 - 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)]. Patients and 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.

AB - 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)]. Patients and 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.

KW - High-grade neuroendocrine carcinoma

KW - Immunohistochemical staining

KW - Lung cancer

KW - Receptor tyrosine kinase

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