Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers.
Summary of "Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers."
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.
Affiliation
Institute for Pathology, Hubertus Wald Tumorzentrum-University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Journal Details
This article was published in the following journal.
Name: Human pathology
ISSN: 1532-8392
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20656317
- DOI: http://dx.doi.org/10.1016/j.humpath.2010.02.018
Medical and Biotech [MESH] Definitions
Genes, Apc
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.
Aberrant Crypt Foci
Clusters of colonic crypts that appear different from the surrounding mucosa when visualized after staining. They are of interest as putative precursors to colorectal adenomas and potential biomarkers for colorectal carcinoma.
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Genes, Mcc
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with the formation of colorectal cancer (MCC stands for mutated in colorectal cancer).
Wolbachia
A genus of bacteria comprised of a heterogenous group of gram-negative small rods and coccoid forms associated with arthropods. (From Bergey's Manual of Systematic Bacteriology, vol 1, 1984)
PubMed Articles
The HER2 protein, encoded by the ERBB2 gene, is a molecular target for the treatment of breast and gastric cancer by monoclonal antibodies or tyrosine kinase inhibitors. While intratumoral heterogenei...
Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome.
Background Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than col...
DNA amplification on chromosome 13q31.1 correlated with poor prognosis in colorectal cancer.
Colorectal cancer is a leading cause of cancer deaths worldwide. Genetic markers involved in prognosis of colorectal cancer are still being elucidated. In this study, genetic alterations associated wi...
Marx A H, Zielinski M, Kowitz C-M, Dancau A-M, Thieltges S, Simon R, Choschzick M, Yekebas E, Kaifi J T, Mirlacher M, Atanackovic D, Brümmendorf TH, Fiedler W, Bokemeyer C, Izbicki J R & Sauter G (20...
Deletion of the long arm of one chromosome 20 (del(20q)) is a well-recognized abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and is presumed to cause loss of a tumor s...
Clinical Trials
Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome
Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary disorder characterized by a very high risk of early-onset colorectal and endometrial cancer and a...
This study is looking at the safety and tolerability of the experimental biological drug EMD 273066 when given with low dose cyclophosphamide to patients with recurring EpCAM positive ovar...
The purpose of the study is to estimate the rate of response for patients with ovarian, non-small cell lung, prostate, colorectal, gastroesophageal, and head and neck cancers who are admin...
The purpose of this study is to evaluate the safety of liver resection for metastatic, resectable lesions from colorectal cancers after systemic chemotherapy.
Level of HER2-neu Gene Amplification an Response to Trastuzumab
Primary objective of the study is to evaluate the correlation between level of HER2-neu gene amplification evalued by dual-color Fluorescent in-situ hybridization (FISH) test and time to p...
