title: Expression site of P2RY12 in residential microglial cells in astrocytomas correlates with M1 and M2 marker expression and tumor grade.
abstract: The role of resident microglial cells in the pathogenesis and progression of glial tumors is still obscure mainly due to a lack of specific markers. Recently P2RY12, a P2 purinergic receptor, was introduced as a specific marker for microglial cells under normal and pathologic conditions. Here we analyzed the expression of P2RY12 in astrocytomas of various malignancy grades in relation to markers for M1 and M2 macrophage activation profiles by using two web-based glioma datasets and confocal immunohistochemistry to 28 astrocytoma samples grades II-IV. In the gliomas, P2RY12 immunoreactivity delineated CD68 negative cells with otherwise microglial features from CD68 positive tumor associated macrophages (TAMs). The presence of P2RY12 positive cells correlated positively with overall survival. P2RY12 mRNA levels and membrane-bound localization of P2RY12 were inversely correlated with increasing malignancy grade, and the expression site of P2RY12 shifted from cytoplasmic in low-grade gliomas, to nuclear in high-grade tumors. The cytoplasmic expression of P2RY12 was associated with the expression of M1 markers, characteristic of the pro-inflammatory macrophage response. In contrast, the nuclear localization of P2RY12 was predominant in the higher graded tumors and associated with the expression of the M2 marker CD163.We conclude that P2RY12 is a specific marker for resident microglia in glioma and its expression and localization correspond to tumor grade and predominant stage of M1/M2 immune response.
authors.affiliation: Department of pathology, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Rotterdam, The Netherlands.
authors.forename: Changbin
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of pathology, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Rotterdam, The Netherlands.|Brain center, Erasmus University Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.affiliation: Department of pathology, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: van der Weiden
authors.affiliation: Department of pathology, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Rotterdam, The Netherlands.
authors.forename: PingPin
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of Nephrology and Hypertension, DIGD, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of pathology, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Rotterdam, The Netherlands. d.mustafa@erasmusmc.nl.|Brain center, Erasmus University Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. d.mustafa@erasmusmc.nl.
authors.forename: Dana A M
authors.initials: DA
authors.lastname: Mustafa
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D014408:Biomarkers, Tumor / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D016208:Databases, Factual; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D008875:Middle Aged; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000378:metabolism; D017423:Sequence Analysis, RNA; D016019:Survival Analysis; D016896:Treatment Outcome; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Glioblastoma; Glioma; Immunohistochemical markers; Microglia; TAM