Immunophenotypic Identification and Characterization of Tumor Cells and Infiltrating Cell Populations in Meningiomas

• DOI: 10.1016/j.ajpath.2012.07.033
• Publication Date: 2012-09-13T18:17:48Z
• Authors: Patrícia H. Domin...; Cristina Teodósio; Javier Ortiz; Pablo Sousa; Álvaro Otero; Angel Maillo; Paloma Bárcena; Maria C. García-M...; Maria C. Lopes; Catarina de Oliveira; Alberto Orfao; Maria D. Tabernero
• Keywords: Adult; Aged, 80 and over; Male; 0303 health sciences; Gene Expression Profiling; Middle Aged; Flow Cytometry; Cell Compartmentation; Immunophenotyping; Neoplasm Proteins; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Phagocytosis; Meningeal Neoplasms; Humans; Female; RNA, Messenger; Meningioma; Aged

Meningiomas are primary tumors of the central nervous system composed of both neoplastic and other infiltrating cells. We determined the cellular composition of 51 meningioma samples by multiparameter flow cytometric (MFC) immunophenotyping and investigated the potential relationship between mRNA and protein expression levels of neoplastic cells. For immunophenotypic, morphologic, and cytogenetic characterization of individual cell populations, a large panel of markers was used together with phagocytic/endocytic functional assays and MFC sorting. Overall, our results revealed coexistence of CD45(-) neoplastic cells and CD45(+) immune infiltrating cells in all meningiomas. Infiltrating cells included tissue macrophages, with an HLA-DR(+)CD14(+)CD45(+)CD68(+)CD16(-/+)CD33(-/+) phenotype and high phagocytic/endocytic activity, and a small proportion of cytotoxic lymphocytes (mostly T CD8(+) and natural killer cells). Tumor cells expressed multiple cell adhesion proteins, tetraspanins, HLA-I/HLA-DR molecules, complement regulatory proteins, cell surface ectoenzymes, and growth factor receptors. Noteworthy, the relationship between mRNA and protein levels was variable, depending on the proteins evaluated and the level of infiltration by immune cells. In summary, our results indicate that MFC immunophenotyping provides a reliable tool for the characterization of the patterns of protein expression of different cell populations coexisting in meningioma samples, with a more accurate measure of gene expression profiles of tumor cells at the functional/protein level than conventional mRNA microarray, independently of the degree of infiltration of the tumor by immune cells.