Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1.
The incidence and association with 10-year survival of amplification in five protooncogenes or transforming genes were retrospectively examined using DNAs extracted from formalin-fixed, paraffin-embedded blocks of tissues obtained from 176 consecutive patients surgically treated for primary breast carcinoma. The incidences of greater than threefold amplification of hst-1, int-2, c-erbB-2, ear-1 (one of c-erbA), and c-myc were 12, 13, 16, 10, and 4.0%, respectively. hst-1 and int-2 were almost always coamplified (21/22), while c-erbB-2 and ear-1 were frequently coamplified (18/28) with almost the same copy number. The hst-1 and int-2 pair and the c-erbB-2 and ear-1 pair, localized on chromosomes 11q13 and 17q21-22, respectively, in normal cells, were inferred to be constituents of different amplification units. Amplification of hst-1 and/or int-2 was detected preferentially in the younger age group, and was correlated with poorer prognosis in cases carrying four or more copies of the genes. Amplification of c-erbB-2 and/or ear-1 was strongly correlated with poor prognosis in all 176 patients, especially those with lymph node metastasis. Amplification of c-myc was also correlated with poor prognosis. Cox's life-table regression analysis showed that amplification of c-erbB-2 had a prognostic value, which was independent of other known prognostic factors such as lymph node status and tumor size.
Tsuda
H
H
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Hirohashi
S
S
Shimosato
Y
Y
Hirota
T
T
Tsugane
S
S
Yamamoto
H
H
Miyajima
N
N
Toyoshima
K
K
Yamamoto
T
T
Yokota
J
J
D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D009367:Neoplasm Staging; D009857:Oncogenes; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D013997:Time Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D051153:Wnt Proteins; D029961:Zebrafish Proteins