Close association between HER-2 amplification and overexpression in human tumors of non-breast origin.
The relationship between HER-2 overexpression and gene amplification is well evaluated in breast cancers but remains unclear or controversial in many other tumor entities. Therefore, we tested the HER-2 status in more than 120 different tumor entities. 5751 tumor samples were analyzed on TMAs by immunohistochemistry (Hercept-Test, DAKO) and fluorescence in situ hybridization (PathVysion, Abbott-Vysis) under highly standardized conditions. HER-2 overexpression (score 2/3+) and amplification occurred most often in breast cancers but was also seen in 18 other tumor entities including cancers of the urinary bladder (amplification in 14.3%, overexpression in 6.7%), stomach (8.3/4.9%), endometrium (6.6/6.8%), lung (2.8/3.1%) and ovary (2.3/1.2%). Remarkably, a strong association between overexpression and amplification was seen in all examined cancer entities. Trastuzumab therapy is highly efficient in HER-2 amplified breast cancer both in metastatic disease and as an adjuvant therapy. A variety of other tumor entities including frequent neoplasms and cancers with often limited therapeutic options have similar patterns of HER-2 alterations as observed in breast cancer (ie high overexpression due to high level gene amplification). Such tumor entities should be carefully evaluated for a possible utility of trastuzumab treatment.
Tapia
Coya
C
Institute of Pathology, University of Basel, Basel, Switzerland.
Glatz
Katharina
K
Novotny
Hedvika
H
Lugli
Alessandro
A
Horcic
Milo
M
Seemayer
Christian A
CA
Tornillo
Luigi
L
Terracciano
Luigi
L
Spichtin
Hanspeter
H
Mirlacher
Martina
M
Simon
Ronald
R
Sauter
Guido
G
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab