6.3. Gelatinases in a pediatric ALL

In pediatric cases, both MMP-2 and MMP-9 were expressed rarely, as only 12.7% of the cases showed MMP-2 or MMP-9 expression in their blast cells. None of the few patients with CNS or testicular involvement showed positive staining with antibodies for these MMPs. The intensity of pediatric ALL treatment as well as the administration of prophylactic CNS treatment is risk-adapted. It is possible that the more intensive treatments of the high-risk MMP-positive ALL patients obscured the risk of invasive recurrence in these patients. There were more FAB L2 diseases among the MMP-positive cases, which difference was statistically highly significant. This is in accordance with the finding that MMP expression is more common in the adult population, just as FAB class 2 disease is more common in adult than pediatric patients. These findings support the hypothesis that adult and pediatric ALLs are biologically distinct diseases.

This series included three pediatric patients with an invasive pattern of spread, who had negative MMP stainings in their blast cells. This may be explained by the theories of complex interactions between tumor cells and the surrounding matrix during the invasion processes. For example, an animal model of human lymphoma implanted in SCID mouse lymphoma cells used the MMP synthesized by mouse endothelial cells during the invasion into the CNS (Kossakowska et al. 1999). Another possible explanation for the rare occurrence and lack of predictive power of MMP expression might be age. MMP-2 is known to be involved in numerous processes of extracellular matrix remodeling and growth. As there is continuous growth and remodeling during childhood, it could be that MMP expression is under stricter control during the years of growth, and this control could also affect the malignant cells and downregulate their MMP expression in situations other than invasion. However, there are no data in the literature dealing with this issue.

In childhood ALL, the expression of gelatinases is rare and it seems that their immunocytochemical detection provides no information in addition to that obtained by routine modern diagnostic work-up that could be used in the choice of treatment.