Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: An immunohistochemical and chromogenic in situ hybridization study

Jinru Shia, David S. Klimstra, Allan R. Li, Jing Qin, Leonard Saltz, Julie Teruya-Feldstein, Muzaffar Akram, Young Chung Ki, Davis Yao, Philip B. Paty, William Gerald, Beiyun Chen

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Recent data suggest that detection of epidermal growth factor receptor protein by immunohistochemistry (IHC) does not predict response to the antiepidermal growth factor receptor drug, cetuximab, in patients with colorectal carcinoma. In searching for foundation for further investigation to optimize patient selection for cetuximab therapy, this study sought to exploit the tissue microarray and chromogenic in situ hybridization techniques to evaluate the status of epidermal growth factor receptor gene amplification in colorectal cancer and its relationship with protein expression by IHC. The study included 158 primary or metastatic colorectal adenocarcinomas. Immunohistochemical results were scored as 0-3+ based on the intensity of membrane staining. The in situ hybridization signals were counted in 30 nuclei per tissue core. Overall, the rate of tissue loss was 7%, yielding 147 analyzable cases: 123 primary, 24 metastatic. Positive immunohistochemical staining of any intensity was detected in 85% (105/123) of primary and 79% (19/24) of metastatic tumors, whereas gene amplification (>5 gene copies/nucleus) was only seen in 12% (15/123) of primary and 8% (2/24) of metastatic tumors. Only 2/15 primary and 1/2 metastatic tumors that showed gene amplification were amplified at a high level (>10 gene copies/nucleus). Although a positive correlation was detected between the intensity of protein expression and the likelihood of gene amplification in both the primary (P=0.01) and the metastatic (P=0.05) tumors, IHC had a low specificity (17% in primary, 23% in metastatic) in predicting gene amplification. Conversely, all tumors that did not express the protein by IHC lacked gene amplification. Thus, this study shows that only a small fraction of epidermal growth factor receptor- positive colorectal carcinomas detected by IHC are associated with gene amplification. Additional studies are needed to determine whether epidermal growth factor receptor gene amplification bears any informative value in predicting response to cetuximab-based therapy.

Original languageEnglish (US)
Pages (from-to)1350-1356
Number of pages7
JournalModern Pathology
Volume18
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

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erbB-1 Genes
Gene Amplification
In Situ Hybridization
Colorectal Neoplasms
Immunohistochemistry
Neoplasms
Epidermal Growth Factor Receptor
Proteins
Staining and Labeling
Growth Factor Receptors
Patient Selection
Genes
Adenocarcinoma
Membranes

Keywords

  • Anti-EGFR therapy
  • Cetuximab
  • Gene amplification

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma : An immunohistochemical and chromogenic in situ hybridization study. / Shia, Jinru; Klimstra, David S.; Li, Allan R.; Qin, Jing; Saltz, Leonard; Teruya-Feldstein, Julie; Akram, Muzaffar; Ki, Young Chung; Yao, Davis; Paty, Philip B.; Gerald, William; Chen, Beiyun.

In: Modern Pathology, Vol. 18, No. 10, 10.2005, p. 1350-1356.

Research output: Contribution to journalArticle

Shia, J, Klimstra, DS, Li, AR, Qin, J, Saltz, L, Teruya-Feldstein, J, Akram, M, Ki, YC, Yao, D, Paty, PB, Gerald, W & Chen, B 2005, 'Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: An immunohistochemical and chromogenic in situ hybridization study', Modern Pathology, vol. 18, no. 10, pp. 1350-1356. https://doi.org/10.1038/modpathol.3800417
Shia, Jinru ; Klimstra, David S. ; Li, Allan R. ; Qin, Jing ; Saltz, Leonard ; Teruya-Feldstein, Julie ; Akram, Muzaffar ; Ki, Young Chung ; Yao, Davis ; Paty, Philip B. ; Gerald, William ; Chen, Beiyun. / Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma : An immunohistochemical and chromogenic in situ hybridization study. In: Modern Pathology. 2005 ; Vol. 18, No. 10. pp. 1350-1356.
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abstract = "Recent data suggest that detection of epidermal growth factor receptor protein by immunohistochemistry (IHC) does not predict response to the antiepidermal growth factor receptor drug, cetuximab, in patients with colorectal carcinoma. In searching for foundation for further investigation to optimize patient selection for cetuximab therapy, this study sought to exploit the tissue microarray and chromogenic in situ hybridization techniques to evaluate the status of epidermal growth factor receptor gene amplification in colorectal cancer and its relationship with protein expression by IHC. The study included 158 primary or metastatic colorectal adenocarcinomas. Immunohistochemical results were scored as 0-3+ based on the intensity of membrane staining. The in situ hybridization signals were counted in 30 nuclei per tissue core. Overall, the rate of tissue loss was 7{\%}, yielding 147 analyzable cases: 123 primary, 24 metastatic. Positive immunohistochemical staining of any intensity was detected in 85{\%} (105/123) of primary and 79{\%} (19/24) of metastatic tumors, whereas gene amplification (>5 gene copies/nucleus) was only seen in 12{\%} (15/123) of primary and 8{\%} (2/24) of metastatic tumors. Only 2/15 primary and 1/2 metastatic tumors that showed gene amplification were amplified at a high level (>10 gene copies/nucleus). Although a positive correlation was detected between the intensity of protein expression and the likelihood of gene amplification in both the primary (P=0.01) and the metastatic (P=0.05) tumors, IHC had a low specificity (17{\%} in primary, 23{\%} in metastatic) in predicting gene amplification. Conversely, all tumors that did not express the protein by IHC lacked gene amplification. Thus, this study shows that only a small fraction of epidermal growth factor receptor- positive colorectal carcinomas detected by IHC are associated with gene amplification. Additional studies are needed to determine whether epidermal growth factor receptor gene amplification bears any informative value in predicting response to cetuximab-based therapy.",
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AU - Saltz, Leonard

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AU - Akram, Muzaffar

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