Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas

Koji Tsuta, Takahiro Mimae, Hiroaki Nitta, Akihiko Yoshida, Akiko M. Maeshima, Hisao Asamura, Thomas M. Grogan, Koh Furuta, Hitoshi Tsuda

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively. IGF-1R expression in non-small cell lung carcinoma was observed in 41.4% of samples and was more prevalent in SCC (69.3%) than in ADC (25.1%), large cell carcinoma (33.3%), and sarcomatoid carcinoma (12.2%) (P <.001). Among ADCs, most mucinous ADCs (75%) showed strong membranous staining with the IGF-1R antibody. Compared with protein expression, IGF-1R gene alteration was rare (8.4%). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (γ = 0.762, P <.001). IGF-1R-positive tumors were more common in smokers (P =.004), and these tumors were larger (P =.006) than the IGF-1R-negative tumors. IGF-1R BISH positivity was not correlated with any clinicopathologic factor. IGF-1R expression and IGF-1R BISH positivity were not correlated with overall survival. IGF-1R is highly expressed in SCC and mucinous ADC, although copy number alterations in the IGF-1R gene were rare. These findings may have important implications for future anti-IGF-1R therapeutic approaches.

Original languageEnglish
Pages (from-to)975-982
Number of pages8
JournalHuman Pathology
Volume44
Issue number6
DOIs
Publication statusPublished - 2013 Jun
Externally publishedYes

Fingerprint

Somatomedin Receptors
Gene Dosage
Non-Small Cell Lung Carcinoma
Proteins
In Situ Hybridization
Large Cell Carcinoma
Squamous Cell Carcinoma
Neoplasms
Adenocarcinoma
Carcinoma
Mucinous Adenocarcinoma
Receptor Protein-Tyrosine Kinases

Keywords

  • Bright-field in situ hybridization
  • Gene copy number
  • Insulin-like growth factor-1 receptor
  • Non-small cell lung carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas. / Tsuta, Koji; Mimae, Takahiro; Nitta, Hiroaki; Yoshida, Akihiko; Maeshima, Akiko M.; Asamura, Hisao; Grogan, Thomas M.; Furuta, Koh; Tsuda, Hitoshi.

In: Human Pathology, Vol. 44, No. 6, 06.2013, p. 975-982.

Research output: Contribution to journalArticle

Tsuta, K, Mimae, T, Nitta, H, Yoshida, A, Maeshima, AM, Asamura, H, Grogan, TM, Furuta, K & Tsuda, H 2013, 'Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas', Human Pathology, vol. 44, no. 6, pp. 975-982. https://doi.org/10.1016/j.humpath.2012.09.002
Tsuta, Koji ; Mimae, Takahiro ; Nitta, Hiroaki ; Yoshida, Akihiko ; Maeshima, Akiko M. ; Asamura, Hisao ; Grogan, Thomas M. ; Furuta, Koh ; Tsuda, Hitoshi. / Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas. In: Human Pathology. 2013 ; Vol. 44, No. 6. pp. 975-982.
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abstract = "Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively. IGF-1R expression in non-small cell lung carcinoma was observed in 41.4{\%} of samples and was more prevalent in SCC (69.3{\%}) than in ADC (25.1{\%}), large cell carcinoma (33.3{\%}), and sarcomatoid carcinoma (12.2{\%}) (P <.001). Among ADCs, most mucinous ADCs (75{\%}) showed strong membranous staining with the IGF-1R antibody. Compared with protein expression, IGF-1R gene alteration was rare (8.4{\%}). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (γ = 0.762, P <.001). IGF-1R-positive tumors were more common in smokers (P =.004), and these tumors were larger (P =.006) than the IGF-1R-negative tumors. IGF-1R BISH positivity was not correlated with any clinicopathologic factor. IGF-1R expression and IGF-1R BISH positivity were not correlated with overall survival. IGF-1R is highly expressed in SCC and mucinous ADC, although copy number alterations in the IGF-1R gene were rare. These findings may have important implications for future anti-IGF-1R therapeutic approaches.",
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