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 language | English |
|---|---|
| Pages (from-to) | 2159-2170 |
| Number of pages | 12 |
| Journal | Journal of Cancer Research and Clinical Oncology |
| Volume | 141 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2015 May 20 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84946476434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946476434&partnerID=8YFLogxK
U2 - 10.1007/s00432-015-1989-z
DO - 10.1007/s00432-015-1989-z
M3 - Article
C2 - 25989941
AN - SCOPUS:84946476434
VL - 141
SP - 2159
EP - 2170
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
SN - 0171-5216
IS - 12
ER -