A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

Authors

  • Birgitte Vrou Offersen Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
  • Jan Alsner Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
  • Karen Ege Olsen Institute of Pathology, Odense University Hospital, Odense, Denmark
  • Rikke Riisbro Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark
  • Nils Brünner Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark
  • Flemming Brandt Sørensen Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark
  • Boe Sandahl Sørensen Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
  • Birgitte Olrik Schlemmer Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
  • Jens Overgaard Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark

DOI:

https://doi.org/10.1080/02841860801958295

Abstract

Background. The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. Materials and methods. Tumour sections were stained for HER2, CD34, and MIB-1. HER2 scores were based on staining intensity, 3+ being considered HER2+. Angiogenesis was scored by the Chalkley method. MIB-1 was evaluated using systematic random sampling. PAI-1 was measured by ELISA. TP53 mutations were evaluated by DGGE analysis and DNA sequencing. Results. Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0–90 ng/mg protein), 5.00 (range, 2.67–12.00) and 15% (range, 1–83%). MIB-1 was correlated with HER2+, Chalkley counts, TP53 mutations (all p <0.0001), and PAI-1 (p =0.002). In univariate analyses with DSS as endpoint, HER2+ (p <0.0001), mutated TP53 (p <0.0001), high Chalkley (p =0.008), MIB-1 (p =0.002), tumour size (p =0.008), grade (p <0.0001), negative estrogen receptor (p =0.0001), and lymph node status (p <0.0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p <0.0001), MIB-1 (p =0.01), Chalkley scores (p =0.007), negative estrogen receptor (p <0.0001) and grade (p =0.001) indicated poor prognosis. In multivariate analysis, metastatic nodes (1–3 positive: RR 1.56 95% CI 1.02–2.38; >3 positive: RR 3.70 95% CI 2.54–5.38), HER2+ (RR 1.91, 95% CI 1.35–2.70), mutated TP53 (RR 1.70, 95% CI 1.21–2.38), PAI-1 (RR 1.04, 95% CI 1.01–1.07) and grade 3 (RR 1.96, 95% CI 1.83–3.22) were independent markers of poor outcome. Conclusion. Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status.

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Published

2008-01-01

How to Cite

Vrou Offersen, B. ., Alsner, J. ., Ege Olsen, K. ., Riisbro, R. ., Brünner, N. ., Brandt Sørensen, F. ., … Overgaard, J. . (2008). A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer. Acta Oncologica, 47(4), 618–632. https://doi.org/10.1080/02841860801958295

Issue

Vol. 47 No. 4 (2008): Acta Oncologica

Section

Articles