Critical determination of the frequency of c-erbB-2 amplification in breast cancer.
Tissues from 323 methacarn-fixed and paraffin-embedded breast cancers were assessed for c-erbB-2 gene amplification by differential polymerase chain reaction (dPCR). The sensitivity of dPCR was ascertained using cell lines with c-erbB-2 amplification, and the relationship between dPCR ratio value and gene copy number was established. In clinical material the technique was not affected by the DNA contribution of normal tissue elements or by cancer DNA ploidy change. c-erbB-2 gene amplification was detected in 55% of invasive cancers and in 66% of in situ cancers. c-erbB-2 protein overexpression in breast cancer cells, as determined by specific immunohistochemistry, was only detected in 11% of invasive cancers and 43% of in situ cancers. Comparisons show that a substantial number of cancers with c-erbB-2 amplification lack detectable protein overexpression. This illustrates the complex nature of c-erbB-2 gene disregulation in cancer and suggests that multiple combinations of biological events and consequences are possible.
Hubbard
A L
AL
Department of Pathology, University of Edinburgh, Medical School, UK.
Doris
C P
CP
Thompson
A M
AM
Chetty
U
U
Anderson
T J
TJ
D000368:Aged; D001483:Base Sequence; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005069:Evaluation Studies as Topic; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases; D015203:Reproducibility of Results
D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases