The Interaction between Mitotic Index and Bcl2 Expression Provides an Improved Separation Method for Determining Clinical Outcome Compared to Nottingham Histological Grading System (NGS)
TMA Abdel-Fatah, DG Powe, G Ball, JS Reis-Filho, AR Green, IO Ellis. School of Molecular Medical Sciences and Nottingham University Hospitals Trust, University of Nottingham, Nottingham, United Kingdom; Nottingham Trent University, Nottingham, United Kingdom; Institute of Cancer Research, London, United Kingdom
Background: We hypothesised that the interaction between mitotic index (M) and Bcl2 accurately discriminates between low and high-grade breast cancer (BC) and provides a more objective measure of clinical outcome than histological grade especially for patients with small size and oestrogen receptor (ER) negative cancers.
Design: Two independent series of 1650 and 245 invasive BC with long term follow up were subjected to immunohistochemical analysis with antibodies against apoptosis and cell cycle-related proteins. Mitotic index (M) was assessed according to Nottingham Grading System (NGS): M1: <10 mitoses; M2: 10 to 18 mitoses; M3: > 18 mitoses. Subsequently, BC were classified according to the combined M/Bcl2 profile and compared to NGS.
Results: In multivariate Cox regression models including validated prognostic factors, the subgroups defined by M/Bcl2 profile performed better than lymph node status and tumour size. Incorporation of the M/Bcl2 profile into the Nottingham Prognostic Index (NPI) accurately reclassified twice as many patients into the excellent prognosis group, improving decision-making for which patients should be spared systemic adjuvant therapy. Patients with M2-3/Bcl2- and M3/Bcl2+ (high risk) had a 2-3 fold increase in the risk of recurrence when treated with either adjuvant hormone therapy or anthracycline-based chemotherapy than those with M1/Bcl2± and M2/Bcl2+ (low risk) (HR= 3.4 (2.8-5.6); p<0.0001 and HR=2.3 (1.2-4.3); p=0.0009).
Conclusions: In conclusion a grading system defined by mitotic counting and Bcl2 expression accurately reclassified patients with NGS-G2, small size cancers or ER negative into two groups: low risk (NGS-G1 like) versus high risk (NGS-G3 like) of both BC mortality and recurrence, improving prognosis and therapeutic planning.
Tuesday, March 23, 2010 1:15 PM
Platform Session: Section B, Tuesday Afternoon