Figure 1.
Angiotropism and gene expression in primary CNS lymphoma. (A) Angiotropic growth pattern in primary CNS lymphoma. Hematoxylin and eosin stain were used. Specimens used for gene expression analysis in this study were more highly cellular, consisting of at least 70% tumor cells. (B) Distinctions in gene expression between CNS lymphoma and nodal large B-cell lymphoma. Transcriptional profiles of 23 specimens of primary CNS lymphomas were compared with 3 specimens of nonneoplastic brain and with 9 consecutive specimens of large B-cell lymphoma obtained from lymph nodes. Only genes differentially expressed with a false discovery rate less than 0.01 are shown. The samples are clustered within molecular subtypes and ordered by the subtype. The image reveals distinct patterns of gene expression between CNS lymphomas and nodal lymphomas. Each column represents an individual tumor, and each row represents a single gene. Red indicates up-regulation; green, down-regulation; and black, similar to the median of the reference pool. (C) Assignment of PCNSL and nodal DLBCL tumors to germinal center (GCB), activated B cell (ABC), and type 3 subclasses. PCNSL tumors were distributed equally among the 3 subclasses. Hierarchic clustering was based upon the expression of 38 established marker genes of ABC and GCB subtypes. (D) Mean expression of 4 marker genes distinguishes CNS lymphoma as determined by quantitative real-time PCR in cases of primary CNS lymphomas (blue), large B-cell lymphomas from lymph nodes (red), and secondary CNS lymphomas (metastatic CNS lymphomas; yellow). Y-axis corresponds to percent expression of control gene. Error bars depict standard deviation of mean value. P values refer to the differences in expression between primary CNS lymphomas and nodal large B-cell lymphoma: XBP-1 (P < .001), c-Myc (P < .001), PIM-1 (P < .001), and E2F-5 (P < .001). CD10 expression was similar in the 3 types of lymphomas. Gene expression values obtained by microarray analysis were in agreement with those obtained by quantitative RT-PCR. (The minimum Pearson correlation is 0.65 corresponding to the P value of < .001 for the test of the hypothesis of no association between microarray and Taqman data for these marker genes.)