Affiliations: Departments of Pathology, Stavanger University Hospital, Stavanger, Norway | The Gade Institute, University of Bergen, Norway | Free University, Amsterdam, The Netherlands | Department of Surgery, Stavanger University Hospital, Stavanger, Norway | Institute of Surgical Sciences, University of Bergen, Norway
Note: [] Corresponding author: Prof. Dr. J.P.A. Baak, Department of Pathology, Stavanger University Hospital, Box 8100, 4068 Stavanger, Norway. Tel.: +47 51 519534; Fax: +47 51 519920; E-mail: [email protected].
Abstract: Background: The mitotic activity index (MAI) is a strong prognosticator in node-negative invasive breast cancer patients. Recently, a correlation between the MAI and specific chromosomal aberrations at chromosome 1p was described. Methods: Analysis of MAI, immunohistochemical staining patterns for proliferation-associated phosphohistone H3 (PPH3), phosphorylated ERK1/2, p21, cyclin E, Ki67 and cyclin D1 proteins; and prognosis in 158 adjuvant chemotherapy-treated T1-2N0M0 invasive breast cancer patients, analysis of LOH at 1p31 (including ARHI) using the dinucleotide repeats D1S207, D1S430 and D1S464 in 76 patients. Single and multivariate survival analysis was used to evaluate the importance of the various markers tested. Results: LOH at 1p31 did not correlate with MAI nor provide prognostic information. Phosphohistone H3 was the best prognosticator for patients in all age groups with 20 year distant metastasis free survival of distant metastases 93% vs. 72% respectively (p=0.004, HR=4.5). In multivariate analysis, phosphohistone H3<13 vs. ≥13 exceeded the prognostic value of the mitotic activity index. Conclusions: LOH at 1p31 is common in breast cancer, and correlates with loss of proliferation-associated proteins, but not with MAI, PPH3 or prognosis. PPH3 is the best prognosticator in this study group of adjuvant chemotherapy-treated lymph node-negative breast cancer patients.
Keywords: Breast cancer, proliferation, PPH3, loss of heterozygosity, ARHI
