title: Hypoxia-associated protein expression in primary central nervous system diffuse large B-cell lymphoma: does it predict prognosis?
abstract: Hypoxia-associated proteins are commonly expressed as a consequence of disturbances in microcirculation. However, the clinical relevance of the proteins has never been studied in primary central nervous system lymphoma (PCNSL). The expression of hypoxia-inducible factor 1α (HIF-1α) and its downstream proteins, vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT-1), were evaluated in a central nervous system (CNS) lymphoma xenograft model and in human PCNSL tissue. In the CNS lymphoma xenograft model, the expression of HIF-1α, VEGF, and GLUT-1 co-localized in subsets of lymphoma cells adjacent to necrosis. In tumor specimens from 51 patients with PCNSL, positive HIF-1α staining was found in 26 patients (51.0%), positive VEGF in 30 (58.8%), and positive GLUT-1 in 17 (33.3%), and HIF-1α showed a significant correlation with VEGF (p < 0.05). However, no significant association was seen between hypoxia-associated protein positivity and unfavorable clinical characteristics. Thus, the results failed to show an association with shorter overall survival or time to progression, except that the percentage of lymphoma cells positive for GLUT-1 (>20%) was significantly associated with worse survival. In conclusion, hypoxia-associated proteins were expressed in PCNSL, suggesting a hypoxic microenvironment. However, the prognostic relevance of these proteins for PCNSL was not demonstrated in this study.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Seoul Paik Hospital, Inje University School of Medicine, Seoul, Korea.
authors.forename: Jung A
authors.initials: JA
authors.lastname: Kim
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.forename: Juyoun
authors.initials: J
authors.lastname: Jin
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.forename: Young Hyeh
authors.initials: YH
authors.lastname: Ko
authors.forename: Kihyun
authors.initials: K
authors.lastname: Kim
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A