Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and carcinoma with CNS metastasis

Assessing central nervous system (CNS) involvement in patients with lymphoma or carcinoma is important in determining therapy and prognosis. Progranulin (PGRN) is a secreted glycosylated protein with roles in cancer growth and survival; it is highly expressed in aggressive cancer cell lines and specimens from many cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma [12 with CNS metastasis (CNS ⁺ ); 6 without CNS metastasis (CNS ⁻ )], 21 with carcinomas (10 CNS ⁺ ; 11 CNS ⁻ ), and 191 control patients with non-cancer neurological diseases, and compared PRGN levels among these disease groups. Median CSF PGRN levels in the CNS ⁺ lymphoma group were significantly higher than in the CNS ⁻ lymphoma and control non-cancer groups; and were also significantly higher in the CNS ⁺ carcinoma group than in the CNS ⁻ carcinoma and control groups, except for patients with infectious neurological disorders. Receiver operating characteristic curve analyses revealed that CSF PGRN levels distinguished CNS ⁺ lymphoma from CNS ⁻ lymphoma and non-cancer neurological diseases [area under curve (AUC): 0.969]; and distinguished CNS ⁺ carcinomas from CNS ⁻ carcinomas and non-cancer neurological diseases (AUC: 0.918). We report here, for the first time, that CSF PGRN levels are higher in patients with CNS ⁺ lymphoma and carcinomas compared to corresponding CNS ⁻ diseases. This would imply that measuring CSF PGRN levels could be used to monitor CNS ⁺ lymphoma and metastasis.