Osteopontin and CD44 Immunoexpression in Primary Central Nervous System Lymphoma, and Comparison with Nodal and Extranodal Diffuse Large B-Cell Lymphoma
Ji Yuan, Keni Gu, Suash Sharma. Medical College of Georgia, Georgia Health Sciences University, Augusta, GA; University Hospital, Augusta, GA
Background: Primary central nervous system lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) mostly of non-germinal center-like (non-GCB) type. Osteopontin, recently the most up-regulated gene in PCNSL, contributes to spread of carcinomas and myeloma by binding to CD44 variants (CD44v), especially CD44v6. We studied immuno-expression of osteopontin, and its putative receptor CD44v6 and CD44H in PCNSL.
Design: We studied 49 archival pathology cases, including 20 PCNSL, 12 N-DLBCL, and 17 EN-DLBCL. Immunohistochemical (IHC) staining was performed for osteopontin (OPN), CD44v6, CD44H CD10, BCL-6, MUM-1, and Ki67, semi-quantitatively scored by % positivity of tumor cells (0%, 1-25%= score 1, 26-50%=2, 51-75%=3, and 76-100%=4) and staining intensity (none=0, weak=1; moderate=2; intense=3), and an overall IHC score (OIS) obtained by multiplying % score with intensity score (0 to 12), and correlated with Ki67 indices, and GCB vs. non-GCB types.
Results: OPN nuclear positivity was variably observed in 20 of 20 (100%) PCNSL cases, 16 of 17 (95 %) EN-DLBCL, and 3 of 12 (25%) N-DLBCL. The OIS of OPN in PCNSL (7.0±3.5) and EN- (4.4±4.1) groups was significantly higher than N-DLBCL (0.3±0.6) (p < 0.001). The difference in OPN IHC scores between PCNSL and EN-DLBCL group, was not significant (p=0.053). Of the 16 of 49 cases positive for CD44v6 (33%), 6 were PCNSL, and 5 each EN- and N-DLBCL; no statistical difference was observed. CD44H was positive in all cases except one PCNSL, but without any significant differences across the three groups. When non-GCB was compared with GCB group, only CD44H expression was significantly different, with higher expression in non-GCB (score 12±1.5) than GCB group (9.5± 3.1) (P=0.015); the differences were insignificant for OPN and CD44v6. Neither CD44H nor CD44v6 scores correlated with the OPN expression score or Ki67 index.
Conclusions: Osteopontin immunoexpression was highest in PCNSL (PCNSL > EN-DLBCL > N-DLBCL), suggesting its probable role in its pathogenesis. However, its lack of correlation with CD44v6 excludes any major role of the latter in OPN overexpression in PCNSL. Moreover, no association was observed between proliferative index and expression of OPN, CD44H or CD44v6. The significantly higher CD44H expression in non-GCB than GCB group may contribute to the aggressiveness of the non-GCB DLBCL. Further studies with additional CD44 variants may clarify the prognostic/predictive role of osteopontin in PCNSL.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 278, Monday Morning