title: EGFR and gastrointestinal stromal tumor: an immunohistochemical and FISH study of 82 cases.
abstract: Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. Mutually exclusive KIT or platelet-derived growth factor receptor-alpha mutations are key events in gastrointestinal stromal tumor pathogenesis, and specific treatment targeting KIT/platelet-derived growth factor receptor-alpha activation is available. Epidermal growth factor receptor plays an important role in cancer biology and also constitutes a promising molecular target of therapy. Very few reports have been published in the literature about the relationship between gastrointestinal stromal tumor and epidermal growth factor receptor. The aim of this study was to investigate epidermal growth factor receptor immunohistochemical expression and epidermal growth factor receptor gene amplification in 82 consecutive gastrointestinal stromal tumor cases using tissue microarray technique. Hematoxylin- and eosin-stained sections and clinical information were reviewed, and expression of CD117 (KIT), CD34 and epidermal growth factor receptor was investigated by immunohistochemistry. Epidermal growth factor receptor gene copy number was determined using fluorescence in situ hybridization. Immunohistochemistry revealed that CD117 and CD34 were expressed in 96 and 57% of tumors, respectively. Variable epidermal growth factor receptor protein immunohistochemical overexpression was detected in 96% of gastrointestinal stromal tumor cases, but none of the 75 cases with represented tumor tissue cores and countable fluorescence signals exhibited epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. These results show that there is no correlation between epidermal growth factor receptor protein overexpression by immunohistochemistry and epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. Considering that the mechanisms of epidermal growth factor receptor protein overexpression are not well understood and the possibility that anti-epidermal growth factor receptor therapy may be beneficial for patients with gastrointestinal stromal tumor that overexpresses epidermal growth factor receptor, additional studies are encouraged.
authors.affiliation: Consultoria em Patologia, Botucatu, Sao Paulo, Brazil.
authors.forename: Lisandro F
authors.initials: LF
authors.lastname: Lopes
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bacchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D018952:Antigens, CD34; C512478:EGFR protein, human; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit