Retrospective analysis of P-STAT6 expression as a predictive marker in primary nervous system lymphoma patients assigned to high-dose methotrexate

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8059 Background: Recent immunohistochemical data and gene expression values have demonstrated that a majority of Primary Nervous System Lymphoma (PCNSL) express both bcl-6 as well as MUM-1, suggesting an overlapping histogenetic time slot of B-cell differentiation. In addition, an increased expression of P-STAT6 seems to predict short survival in patients (pts.) treated with high-dose Methotrexate (HD-MTX)-based chemotherapy. To investigate the clinical impact of the P-STAT6 expression in this setting we have analyzed P- STAT6 expression in available tumor tissue blocks of 25 PCNSL pts. treated with HD-MTX who have had follow up for at least 2.5 years. Methods: Immunohistochemistry for P-STAT6 was performed using an indirect immunoperoxidase method. Responses were evaluated according to the International Workshop criteria for PCNSL. Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meier Method. Results: 15 male, 10 female; mean age 52.1 years, were included in the analysis. The immunohistochemical analysis showed three different patterns of P-STAT6 expression: 7 pts. had absent P-STAT6 expression and low tumor cellular density (group A); 8 pts. had sparse positive P-STAT6 expression and low cellular density (group B), 10 pts. had strong P-STAT6 nuclear expression in tumor cells and on vascular endothelia and high cellular density (group C). The overall response rates to treatment (CR+PR) were 83% for both group A and B compared to 5% of group C. Furthermore the pts. with intense P-STAT6 expression experienced an impressive early progression (PFS median 2.5 months) and an OS very short (median 10 months). To date pts. of groups A and B have not reached median OS and PFS. Conclusions: PCNSL pts. with intense P-STAT6 expression experienced short survival when treated with HD-MTX- chemotherapy. No significant financial relationships to disclose.