Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study

• Published in: Modern pathology Vol. 17; no. 8; pp. 895 - 904
• Main Authors: Ooi, Akishi, Takehana, Takuo, Li, Xiaoling, Suzuki, Shioto, Kunitomo, Kazuyoshi, Iino, Hiroshi, Fujii, Hideki, Takeda, Yasuhisa, Dobashi, Yoh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2004; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Breast cancer; Chromosomes; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; EGFR; ErbB Receptors - analysis; ErbB Receptors - genetics; FDA approval; Female; FISH; Gene Amplification; HER-2; Humans; Hybridization; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kinases; Ligands; Lung cancer; Male; Metastasis; Middle Aged; Monoclonal antibodies; Pathology; Protein expression; Proteins; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - genetics; Tumors; United States > US; FISH; colorectal cancer; immunohistochemistry; HER-2; EGFR; gene amplification
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800137

Overexpression of HER-2 and the epidermal growth factor receptor (EGFR) has been observed in many cancers, sometimes accompanied by gene amplification. To assess whether novel chemotherapies targeting these overexpressed proteins may be effective for the treatment of colorectal cancers, we examined the exact frequency of HER-2 and EGFR overexpression, the relationship between gene amplification and protein expression, and the heterogeneity of gene amplification within and between primary and metastatic tumors. We evaluated 244 colorectal cancers immunohistochemically. All tumors found to overexpress HER-2 or EGFR were further analyzed for gene amplification by fluorescent in situ DNA hybridization. Overexpression of HER-2 and EGFR was found in 8 (3%) and 19 (8%) of the 244 colorectal carcinomas, respectively. Gene amplification was observed in 100 and 58% of the tumors exhibiting HER-2 and EGFR overexpression, respectively. HER-2 amplification in cancer cells was characterized by clusters of hybridization signals, suggesting amplicons in homogeneously staining regions that were predominant in most primary and metastatic tumors. EGFR amplification, observed as scattered signals reminiscent of amplicons in double minute chromosomes, or coamplification of EGFR with the centromeric regions was observed as a minor population within primary tumors, and found in variety of populations in metastatic tumors. Overexpression of HER-2 and EGFR were observed in only a small fraction of colorectal carcinomas, but were frequently accompanied by gene amplification.