title: Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers.
abstract: HER-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-HER-2 therapy is currently investigated in several other HER-2 amplified cancers. For example, trastuzumab was recently shown to be effective in HER-2 positive gastric cancer. To address the potential applicability of anti-HER-2 therapy in colorectal cancer, tissue microarray sections and colorectal resection specimens of 1851 colorectal cancers were analyzed for HER-2 overexpression and amplification using FDA approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 2.5% and HER-2 overexpression in 2.7% of 1439 interpretable colorectal cancers. Amplification was often high level with HER-2 copies ranging from 4 to 60 per tumor cell and was strongly related to protein overexpression. HER-2 amplification and overexpression were unrelated to histological tumor type, tumor localization, grading, pT, pN, pM or survival. As heterogeneity of drug target expression could represent a major drawback for targeted cancer therapy we next studied HER-2 heterogeneity in selected cases. Extensive evaluation of all available large sections from patients with HER-2 positive colorectal cancer revealed heterogenous findings in 3 of 4 cases. In summary, high-level HER-2 amplification occurs in a small fraction of colorectal cancers. Heterogeneity of amplification may limit the utility of anti- HER-2 therapy in some of these tumors and therefore, adequate clinical trials are needed to further evaluate this approach.
authors.affiliation: Institute for Pathology, Hubertus Wald Tumorzentrum-University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. a.marx@uke.de
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Marx
authors.forename: Eike C
authors.initials: EC
authors.lastname: Burandt
authors.forename: Matthias
authors.initials: M
authors.lastname: Choschzick
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Emre
authors.initials: E
authors.lastname: Yekebas
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human