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
✍ Scribed by Olli-P. Kallioniemi; Kaija Holli; Tapio Visakorpi; Timo Koivula; Heikki H. Helin; Jorma J. Isola
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 818 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
C‐__erb__B‐2 protein over‐expression was studied immunohis‐tochemically 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‐__erb__B‐2 was optimized using protease pre‐treatment and verified using antibodies for both the external and the internal domains of the protein. c‐__erb__B‐2 over‐expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade (p < 0.0001), DNA aneuploidy (p = 0.003), high tumor S‐phase fraction (p < 0.000l), and lack of estrogen (p < 0.0001) and progesterone (p = 0.03) receptors. Overall, breast‐cancer patients with c‐__erb__B‐2 over‐expression had about 2.2‐fold relative risk (RR) of death (p < 0.001) as compared with those without over‐expression. According to a multivariate analysis, c‐__erb__B‐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‐__erb__B‐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‐__erb__B‐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‐__erb__B‐2 over‐expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.