The Expression of Progenitor Cell Markers in Primary Central Nervous System Lymphoma: Role of SOX2/OCT4 in Lymphomas with B-Cell Phenotype
Gulen Gul Niflioglu, Melike Pekmezci, Ellen F Krasik, Tarik Tihan. Dokuz Eylul University, Izmir, Turkey; University of California San Francisco, San Francisco, CA
Background: Primary central nervous system lymphoma (PCNSL) is typically a diffuse large B-cell lymphoma (DLBCL) and factors associated with its prognosis have not been clearly identified. In recent studies, SOX2-OCT4 pathway has been found to be highly active in cancers of the prostate, stomach, breast, colon, brain and testis and most of these reports focus on the correlation between SOX2 expression and various clinicopathological parameters. To the best of our knowledge, the role of SOX2-OCT4 pathway in the biology of DLBCL is not clear and SOX2/OCT4 expression have not been studied in PCNSL. Based on recent studies on CNS neoplasia, we have hypothesized that SOX2-OCT4 pathway may be active in PCNSL.
Design: We reviewed all patients with DLBCL of the CNS diagnosed at our institution during the last 15 years. All available specimens were stained with CD10, Bcl6 and MUM1 to evaluate DLBCL subtype and with SOX2 and OCT4 using commercially available antibodies. The results were analyzed in the light of clinical features.
Results: We included 115 patients in the study. Seventy patients (37 male, 33 female) had DLBCL with no evidence of systemic involvement or immunosuppression and were considered in the PCNSL category. Eighteen patients had HIV/AIDS (15 male, 3 female) and were included in the HIV category. Five patients (1 male, 4 females) had monomorphic B-cell post-transplant lymphoproliferative disorder. The remaining 22 patients (9 males, 13 females) had systemic DLBCL with secondary CNS involvement. Immunophenotypic profiling performed in 32 cases (16 PCNSL, 7 HIV, 9 systemic,) revealed that 23 non-germinal centre and 9 germinal centre type. Almost all cases stained with the SOX2 antibody (>95%) showed diffuse strong nuclear positivity and rare tumors (<10%) in the germinal center type demonstrated strong OCT4 positivity.
Conclusions: This study provides preliminary evidence that the SOX2-OCT4 pathway may be involved in DLBCL of the CNS. While the practical implications and the diagnostic utility of this staining pattern remains to be determined, the strong SOX2 positivity along with only rare OCT4 positive cases imply that SOX2/OCT4 may be altered in DLBCL and this alteration may involve different mechanisms. This is particularly interesting in the light of earlier studies that demonstrate expression of SOX2 to be inversely related to normal hematogenic potency.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 247, Wednesday Afternoon