CCR7 Expression Is Not a Useful Clinical Marker for CNS Involvement in T Lymphoblastic Leukemia/Lymphoma.
David C Spence, Eric Duncavage, Sheryl Tripp, Albert Ho, Sherrie Perkins. SUNY Upstate Medical University, Syracuse, NY; University of Utah, Salt Lake City
Background: T lymphoblastic leukemia/lymphoma(T-ALL/L) comprises approximately 15% of pediatric lymphoblastic leukemias. Compared to B-ALL/L, these patients have an increased risk of CNS involvement generally requiring CNS irradiation and intrathecal chemotherapy with considerable side effects. Recently Buonamici et al. demonstrated that CCR7, a chemokine receptor (CD197) expressed on both T and B cells, was essential for CNS involvement by T-ALL/L in a mouse model. Using human cell lines, they showed that CCR7 negative T-ALL/L was unable to involve the CNS. In this study we investigate the clinical utility of CCR7 expression by immunohistochemistry (IHC) as a method to predict CNS involvement.
Design: We identified 40 unique cases of pediatric and young adult T-ALL/L (<22 years old) for which archival bone marrow cores or clots and adequate clinical information were available. These cases had a median blast percentage of 73.5% and included eight cases with documented CNS involvement. Slides were stained with mouse anti-human CCR7 antibody (Abcam: ab1657) and read by two study pathologists to determine the number of cells positive for CCR7 and relative staining intensity. To confirm that CCR7 was in fact expressed by the blast population we further performed dual color IHC using alk phos-labeled CCR7 and HRP-labeled TdT on a subset of cases.
Results: Dual-color IHC staining demonstrated co-expression of CCR7 and TdT in the majority of cells, confirming expression of CCR7 in the blast population. All cases of T-ALL/L showed a high percentage of lymphoblasts (>90% average) that were strongly positive (3+ of 3) for CCR7 expression. A comparison of CCR7 expression in decalcified bone marrow cores versus clots showed no difference. No significant correlation was identified with CCR7 expression and CNS disease at presentation or relapse.
Conclusions: We demonstrate that CCR7 is highly expressed in lymphoblasts in all tested cases of T-ALL/L and has no correlation with subsequent CNS involvement in this study set. In contrast to previously published studies, that examined only small number of patients, we did not identify any CCR7 negative cases, despite 20% of patients having documented CNS involvement. We cannot exclude, however, that more sensitive methods such as flow cytometry might be capable of discriminating between different intensity levels of CCR7 expression. Therefore, the measurement of CCR7 expression by IHC is not a clinically useful marker of CNS involvement by T-ALL/L.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 166, Tuesday Afternoon