Preferential up-regulation of osteopontin in primary central nervous system lymphoma does not correlate with putative receptor CD44v6 or CD44H expression

Abstract

Osteopontin (SPP1) is reportedly the most up-regulated gene in primary central nervous system lymphoma (PCNSL). Our objective was to confirm immunoexpression of osteopontin and determine if CD44v6 and CD44H played a significant role as receptors for osteopontin in PCNSL. Twenty PCNSL, 12 nodal diffuse large B-cell lymphoma (N-DLBCL), and 17 extra-nodal DLBCL (EN-DLBCL) archival pathology cases were examined. Osteopontin nuclear positivity was observed in 20 (100%) of 20 PCNSL cases, 16 (95 %) of 17 EN-DLBCL, and 3 of 12 (25%) N-DLBCL. The immunohistochemical score of osteopontin in PCNSL (7.0 ± 3.5) and EN-DLBCL (4.4 ± 4.1) was significantly higher than N-DLBCL (0.3 ± 0.6). Sixteen cases were positive for CD44v6 (33%), including 6 PCNSL, and 5 each EN-DLBCL and N-DLBCL; no statistical difference was observed. CD44H was positive in all cases except one PCNSL but without any significant differences across the 3 groups. CD44H expression was significantly higher in non-germinal center B-cell (GCB) (score 12 ± 1.5) as compared to the GCB group (9.5 ± 3.1), and in non-GCB PCNSL (7.9 ± 4.2) as compared to non-GCB non-CNS lymphoma (2.8 ± 4.0) (P = .009); the differences were insignificant for osteopontin and CD44v6. Neither CD44H nor CD44v6 scores correlated with the osteopontin expression score or Ki-67 index. Osteopontin immunoexpression was highest in PCNSL, suggesting its probable role in its pathogenesis. However, its lack of correlation with CD44v6 excludes the latter as the likely osteopontin receptor in PCNSL. The significantly higher CD44H expression in the non-GCB than GCB group may contribute to the aggressiveness of the non-GCB DLBCL. Further studies are needed to elucidate the pathway and the prognostic/predictive role of osteopontin in PCNSL.