Tumour Infiltration by CD8+ T Lymphocytes Is Associated with Patient Outcome in Breast Cancer
SM Mahmoud, K Baker, AR Green, EC Paish, AHS Lee, WD Foulkes, IO Ellis. School of Molecular Medical Sciences, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom; McGill University, Montreal, QC, Canada
Background: Tumour-related antigens can be recognised by cytotoxic T lymphocytes (CTLs) in the context of MHC class I-expressing tumours. Immunohistochemical identification of CD8+ T lymphocytes has been recently correlated to an improved overall survival in colorectal, ovarian, renal, and oesophageal carcinomas. The prognostic significance of CD8+ T-cells in breast cancer has been studied in relatively small numbers of patients and the available reports do not have comprehensive data about different localisation patterns and long-term follow-up.
Design: We have assessed the expression of tumour-infiltrating CD8+ T-cells using immunohistochemistry of tissue microarray preparations from a large cohort of 957 unselected breast cancer cases with long-term follow up and investigated the relationship with clinical outcome.
Results: CD8+ lymphocytes were identified in 510 cases (54%), 392 cases (41%) were positive for intratumoural CD8+ T-cells and 320 cases (33%) were positive for stromal CD8+ T-cells. Tumours were divided into 4 groups according to the expression and localisation of CD8+ cells; negative tumours (contained no CD8+ cells, n= 447), tumours contained only intratumoural CD8+ cells (defined as cases with CD8+ cells touching tumour cells, n= 190), tumours contained only stromal CD8+ cells (n= 118), and tumours contained CD8+ cells in both compartments (n= 202). Patients with only stromal CD8+ T-cell in their tumours showed a significant association with the best breast cancer specific survival (BCSS, p= 0.005) and the longest disease free interval (DFI, p= 0.001). This effect was retained in ER+ and HER-2+ tumour subgroups. In contrast, the subgroup with only intratumoural CD8+ cells showed the worst prognosis. In multivariate survival analysis including tumour size, stage, grade, and HER-2 status; stromal CD8+ cell expression was an independent predictor of patient outcome.
Conclusions: In conclusion, we have identified that degree and location of CD8+ T lymphoid cells in breast cancer tissue samples influences patient outcome in an independent manner. Further investigation of the functional activity of CD8+ lymphoid cell in breast cancer in general and in its various biological sub groups appears warranted.
Monday, March 9, 2009 1:00 PM
Platform Session: Section B, Monday Afternoon