Classical Hodgkin lymphomas (cHL) are B lympho-proliferative disorders that can be cured in 80% of cases. The goal of current research is to identify, at diagnosis, the 20% patients, who are likely to relapse or be refractory to treatment. As cHL have an extensive micro-environment implicated in tumour growth, the prognostic value (disease-free survival) of 2 important subsets of lymphoid cells (CD45RO+ effector memory T cells and FOXP3+ regulatory T cells) of the micro-environment has been evaluated using Tissue Micro Array (TMA).
Patients (n=96) treated and followed for cHL between 1998 and 2005 were included in this study. Six TMA with 3 spots per case, were built (3 formalin and 3 Bouin fixative). Immunostaining with anti-CD45RO (Dako, UCHL1, 1/400) and anti-FOXP3 (Abcam, 236A/E7 1/100) antibodies was performed on the Benchmark Ultra (Ventana). After scanning of the slides, the staining was quantified automatically using a function (pixel count) of Scanscope software (Aperio). ROC curves were used in order to calculate the best threshold for each marker, depending on the number and intensity of pixels. Survival curves were built according to these thresholds using the Kaplan Meier method and compared with the log-rank test. Then, a Cox model was used to estimate the risk of occurrence of an event in univariate and multivariate analyses.
The demographic characteristics of patients and sub-types of HL were not different in the << formalin >> and << Bouin >> groups. Median follow-up of patients was 69 months (1-135). In univariate analysis, low quantities of CD45RO+ cells was associated to a 40% 5-years progression free survival (PFS) compared to a 87% 5-years PFS for patients with high number of CD45RO+ cells (p=0.003), and low number of FOXP3+ cells was related to a 56% 5-years PFS compared to a 86% 5-years PFS for patients with high number of FOXP3+ cells (p=0.026). In multivariate analysis, taking into account the International Prognostic Score (IPS) and the expression of CD15 by neoplastic cells, the association of CD45RO and FOXP3 was the only independent prognostic factor identified (p<0.02 et RR=5.75).
This preliminary study underlines the importance of certain subsets of cells from the microenvironment of HL in the control of tumour growth. These results are encouraging. When used in association with validated criteria, they could make it possible to identify patients at risk of relapse and/or drug resistance. Nevertheless, due to the small number of patients in our study, these findings need to be validated in a larger and/or independent cohort.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.