Minichromosome Maintenance Protein 2 Is a Strong Independent Prognostic Marker in Breast Cancer

Abstract

Purpose: To test the hypothesis that prognostic information in breast cancer may be derived from an accurate assessment of epithelial cell cycle entry, as indicated by expression of minichromosome maintenance (MCM) proteins.Materials and Methods: We used immunohistochemistry to examine the distribution of Mcm-2 in breast tissue. Power calculations based on a pilot study of 67 whole tissue sections led to selection of an independent 347-core breast carcinoma tissue microarray validation set. We tested for associations between Mcm-2 (and Ki-67) labeling index (LI) and various clinicopathologic parameters.Results: Mcm-2 was expressed more frequently than the standard proliferation marker Ki-67 in whole tissue sections of normal breast (P = .0003) and breast carcinoma (P < .0001). In 221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive association with tumor size (P = .002), mitotic index (P < .0001), histologic grade (P < .0001), and the Nottingham Prognostic Index (NPI) score (P < .0001). Using a cutoff value of 50%, Mcm-2 LI was associated with overall survival (P = .0007), disease-free interval (P = .0002), and with the development of regional recurrence (P = .011) and distant metastases (P = .0016). Cox regression analysis suggested that the Mcm-2 LI is a strong prognostic factor in breast cancer that is independent and superior to histologic grade, lymph node stage, and Ki-67 LI, but not the NPI score.Conclusion: Mcm-2 may be of utility as a prognostic marker to refine the prediction of outcome in breast cancer, for example when combined with parameters currently used in the NPI.