Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer.
c-erbB-2 protein over-expression was studied immunohistochemically in 319 paraffin-embedded breast carcinomas representing 89% of all breast-cancer cases operated in the Tampere University Hospital between 1977 and 1981. The immunohistochemical evaluation of c-erbB-2 was optimized using protease pre-treatment and verified using antibodies for both the external and the internal domains of the protein. c-erbB-2 over-expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade (p less than 0.0001), DNA aneuploidy (p = 0.003), high tumor S-phase fraction (p less than 0.0001), and lack of estrogen (p less than 0.0001) and progesterone (p = 0.03) receptors. Overall, breast-cancer patients with c-erbB-2 over-expression had about 2.2-fold relative risk (RR) of death (p less than 0.001) as compared with those without over-expression. According to a multivariate analysis, c-erbB-2 over-expression was an independent prognostic factor in the whole material as well as in the node-negative sub-set. In node-negative breast-cancer tumor size, S-phase and c-erbB-2 status defined a large patient group with only 4% 5-year and 15% 10-year mortality rate without adjuvant therapy. In comparison with c-erbB-2-negative tumors, those with over-expression of this gene metastasized 3 times more often (p = 0.0002) to the lungs, liver and brain and 3 times less often to the bone. Our findings suggest that the prognostic value of c-erbB-2 over-expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.
Department of Clinical Chemistry, Tampere University Hospital, Finland.
O P
OP
Kallioniemi
K
K
Holli
T
T
Visakorpi
T
T
Koivula
H H
HH
Helin
J J
JJ
Isola
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002455:Cell Division; D004247:DNA / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008593:Menopause; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011003:Ploidies; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases; D012307:Risk Factors; D015996:Survival Rate
D004247:DNA; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases