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Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications

Rudolph, P; Olsson, Håkan LU ; Bonatz, G; Ratjen, V; Bolte, H; Baldetorp, Bo LU ; Fernö, Mårten LU ; Parwaresch, R and Alm, P (1999) In Journal of Pathology 187(2). p.207-276
Abstract
Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size,... (More)
Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size, DNA aneuploidy, lack of steroid hormone receptors, young age, and increased topoisomerase II alpha and Ki-67 expression levels. The correlation of p53 and c-erbB-2 was not significant. Topoisomerase II alpha and Ki-67 scores closely paralleled each other, indicating that both reflect the proliferative activity of tumour cells. A univariate analysis of overall (OS), specific (SS), and disease-free survival (DFS) revealed all the above-mentioned parameters to be statistically significant except patient age, which was relevant only to overall survival. Multivariate analysis with inclusion of all covariates selected tumour size and proliferation (topoisomerase II alpha and Ki-67) indices as independent predictors of survival in all three models. No additional information was gained by p53 or c-erbB-2. It is concluded that the proliferative activity, as assessed by topoisomerase II alpha or Ki-67 immunostaining, is the most useful indicator of breast cancer prognosis, except for tumour size. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, prognosis, proliferation, p53, c-erbB-2, Ki-67, topoisomerase II
in
Journal of Pathology
volume
187
issue
2
pages
207 - 276
publisher
John Wiley & Sons
external identifiers
  • pmid:10365096
  • scopus:0032904256
ISSN
0022-3417
DOI
10.1002/(SICI)1096-9896(199901)187:2<207::AID-PATH223>3.0.CO;2-U
language
English
LU publication?
yes
id
b74d4900-0ba7-45f6-bfc1-6a10c961735c (old id 1114332)
date added to LUP
2008-07-03 16:51:22
date last changed
2017-09-10 03:51:13
@article{b74d4900-0ba7-45f6-bfc1-6a10c961735c,
  abstract     = {Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size, DNA aneuploidy, lack of steroid hormone receptors, young age, and increased topoisomerase II alpha and Ki-67 expression levels. The correlation of p53 and c-erbB-2 was not significant. Topoisomerase II alpha and Ki-67 scores closely paralleled each other, indicating that both reflect the proliferative activity of tumour cells. A univariate analysis of overall (OS), specific (SS), and disease-free survival (DFS) revealed all the above-mentioned parameters to be statistically significant except patient age, which was relevant only to overall survival. Multivariate analysis with inclusion of all covariates selected tumour size and proliferation (topoisomerase II alpha and Ki-67) indices as independent predictors of survival in all three models. No additional information was gained by p53 or c-erbB-2. It is concluded that the proliferative activity, as assessed by topoisomerase II alpha or Ki-67 immunostaining, is the most useful indicator of breast cancer prognosis, except for tumour size.},
  author       = {Rudolph, P and Olsson, Håkan and Bonatz, G and Ratjen, V and Bolte, H and Baldetorp, Bo and Fernö, Mårten and Parwaresch, R and Alm, P},
  issn         = {0022-3417},
  keyword      = {breast cancer,prognosis,proliferation,p53,c-erbB-2,Ki-67,topoisomerase II},
  language     = {eng},
  number       = {2},
  pages        = {207--276},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Pathology},
  title        = {Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications},
  url          = {http://dx.doi.org/10.1002/(SICI)1096-9896(199901)187:2<207::AID-PATH223>3.0.CO;2-U},
  volume       = {187},
  year         = {1999},
}