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.
Highlights
Breast cancer is the most frequent cancer among women in industrialized countries, and the death rate from breast cancer is persistently high
The prognostic value of mitotic activity index (MAI) has been demonstrated in many retrospective and prospective multicenter studies using a fixed threshold (MAI < 10 favorable; MAI 10 unfavorable). These studies showed that MAI is reproducible, stable and robust, despite variations in tissue processing, and is a strong prognosticator in node-negative invasive breast cancer 3 in women under 70 years of age, but not in women over 70 [2]
A tight correlation between phosphorylation of histone H3 (=phosphohistone H3 (PPH3)) and mitotic chromatin condensation has been shown in studies using an antibody selective for the Ser-10 phosphorylated histone H3 (=PPH3)
Summary
Breast cancer is the most frequent cancer among women in industrialized countries, and the death rate from breast cancer is persistently high. One strong, yet simple and reproducible, proliferation-associated prognostic factor is the mitotic activity index (MAI) [4,23]. The prognostic value of MAI has been demonstrated in many retrospective and prospective multicenter studies using a fixed threshold (MAI < 10 favorable; MAI 10 unfavorable) (for a review, see [10]). These studies showed that MAI is reproducible, stable and robust, despite variations in tissue processing, and is a strong prognosticator in node-negative invasive breast cancer 3 in women under 70 years of age, but not in women over 70 [2]. The mitotic activity index (MAI) is a strong prognosticator in node-negative invasive breast cancer patients. A correlation between the MAI and specific chromosomal aberrations at chromosome 1p was described
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