Osteopontin 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, Augusta; University Hospital, Augusta, GA
Background: Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma (DLBCL) mostly of activated B cell type (ABC), with poor prognosis, yet confined to the CNS microenvironment. Osteopontin, a cell-matrix glycoprotein, is associated with progression, metastatic spread and poor prognosis in several tumors. Osteopontin was the most up-regulated gene in PCNSL compared to nodal and extra-nodal DLBCL (N-DLBCL, EN-DLBCL) in recent cDNA microarray studies. We aimed to validate the protein expression of osteopontin and assess its prognostic value in PCNSL.
Design: We retrieved 19 archival cases of PCNSL, 11 N-DLBCL, and 17 EN-DLBCL from pathology records. Immunohistochemical (IHC) staining was performed for osteopontin and Ki67 on formalin-fixed paraffin-embedded sections using Envision Plus System. Staining for osteopontin was semi-quantitatively stratified and scored both by percentage 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 score (0 to 12) calculated for each case by multiplying percentage score with intensity score. This data was correlated with Ki67 proliferative indices.
Results: Osteopontin nuclear immune-expression was observed in 18 of 19 (95%) PCNSL cases, 16 of 17 (95 %) EN-DLBCL, and 3 of 12 (25%) N-DLBCL cases. Staining intensity was moderate to strong in most PCNSL cases (especially intense in perivascular and infiltrating neoplastic cells), but weaker and noted in fewer cases sequentially in the EN- or N-DLBCL groups. The overall immunostaining scores were significantly higher in PCNSL group (6.4 ± 3.6) and in EN- (4.4 ± 4.1) than N-DLBCL (0.3 ± 0.7) groups (p< 0.001). The difference in osteopontin IHC scores between PCNSL and EN-DLBCL group, was however not statistically significant (p=0.09). Further, high osteopontin expression was not associated with high Ki67 proliferation index.
Conclusions: Osteopontin immunoexpression was highest in PCNSL, especially in perivascular and infiltrating neoplastic cells, sequentially followed by EN-DLBCL and N-DLBCL. No association was observed between osteopontin expression levels with proliferative index. Future studies are required to assess the prognostic/predictive role of osteopontin in PCNSL.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 241, Tuesday Afternoon