NEW YORK (Reuters Health) – A new biomarker – tumor-associated CD68+ macrophages — predicts poor outcomes in patients with classic Hodgkin’s lymphoma, new research indicates.
About 20% of patients with Hodgkin’s lymphoma die of progressive disease, including about half of patients treated by autologous hematopoietic stem-cell transplantation. According to the report in the March 11 New England Journal of Medicine, none of the available prognostic-factor scoring systems can reliably identify patients in whom treatment is likely to fail.
To identify potential markers of treatment response, senior author Dr. Randy D. Gascoyne, from the British Columbia Cancer Agency, Vancouver, and associates used gene expression profiling to analyze frozen lymph node specimens from 130 patients.
They found a significant correlation between the gene-expression profile and the outcome of first-line treatment (p = 0.02). Of the potential markers identified, the researchers further analyzed CD68+ macrophages, CD20+ B cells, and matrix metalloproteinase-11 (MMP11) by immunohistochemical staining of samples from an independent cohort of 166 patients.
They found that CD68 “stood out because of its significant correlation” with survival. On a scale of 1 to 3, a score of 3 — representing the highest concentration of CD68+ macrophages — was associated with lower 10-year disease-specific progression free survival (59.6%, compared to 88.6% for a score of 1, p = 0.003), as well an increased likelihood of relapse after stem-cell transplantation (p = 0.008).
In patients with limited-stage disease, a CD68 score of 1 was associated with 100% 10-year disease-specific survival (p = 0.04).
On the other hand, a high-risk International Prognostic Score was not significantly associated with the number of CD68+ macrophages (p = 0.17).
MMP11 correlated with progression-free survival but not with disease-specific survival. CD20+ small B cells were associated with prolonged progression-free survival and disease-specific survival (p = 0.02 for both) but did not independently predict survival.
In conclusion, Dr. Gascoyne and colleagues write, “The CD68+ macrophage content represents a biomarker with clinical applicability in all stages of classic Hodgkin’s lymphoma, both at the time of diagnosis and at the time of relapse.”
They add that CD68 identified by immunohistochemical analysis “can be easily incorporated into a routine diagnostic approach.”
Authors of a related editorial explain that tumor-associated macrophages mediate blood-vessel formation through the secretion of vascular endothelial growth factor and hypoxia-inducing factor.
Drs. Vincent T. DeVita Jr. and Jose Costa from the Yale School of Medicine, New Haven, Connecticut, add that the data presented by Dr. Gascoyne et al could ultimately “bring more logic to the treatment of this curable cancer.”
Reference:
N Engl J Med 2010;362:875-885,942-943.
