title: Flow cytometry analysis of neural differentiation markers expression in human glioblastomas may predict their response to chemotherapy.
abstract: Glioblastoma multiforme (GBM) represents an extremely chemoresistant tumour type. Here, authors analysed the immunophenotype of GBM tumours by flow cytometry and correlated the immunophenotypic characteristics with sensitivity to chemotherapy. The expression of selected neural and non-neural differentiation markers including A2B5, CD34, CD45, CD56, CD117, CD133, EGFR, GFAP, Her-2/neu, LIFR, nestin, NGFR, Pgp and vimentin was analysed by flow cytometry in eleven GBM (WHO gr.IV) patients. The sensitivity of tumour cells to a panel of chemotherapeutic agents was tested by the MTT assay. All tumours were positive for A2B5, CD56, nestin and vimentin. CD133, EGFR, LIFR, NGFR and Pgp were expressed only by minor tumour cell subpopulations. CD34, CD45, CD117, GFAP and Her-2/neu were constantly negative. Direct correlations were found between the immunophenotypic markers and chemosensitivity: A2B5 vs lomustine (r(2) = 0.642, P = 0.033), CD56 vs cisplatin (r(2) = 0.745, P = 0.013), %Pgp(+) vs vincristine (r(2) = 0.846, P = 0.008), and %NGFR(+) vs daunorubicine (r(2) = 0.672, P = 0.047) and topotecan (r(2) = 0.792, P = 0.011). In contrast, inverse correlations were observed between: EGFR vs paclitaxel (r(2) = -0.676, P = 0.046), CD133 vs dacarbazine (r(2) = -0.636, P = 0.048) and LIFR vs daunorubicine (r(2) = -0.878, P = 0.004). Finally, significant associations were also found among sensitivities to different chemotherapeutic agents and among different immunophenotypic markers. In conclusion, histopathologically identical GBM tumours displayed a marked immunophenotypic heterogeneity. The expression of A2B5, CD56, NGFR and Pgp appeared to be associated with chemoresistance whereas CD133, EGFR and LIFR expression was characteristic of chemosensitive tumours. We suggest that flow cytometric imunophenotypic analysis of GBM may predict chemoresponsiveness and help to identify patients who could potentially benefit from chemotherapy.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine and Louis Pasteur University Hospital, PJ Safarik University, Kosice, Slovak Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Balik
authors.forename: Peter
authors.initials: P
authors.lastname: Mirossay
authors.forename: Peter
authors.initials: P
authors.lastname: Bohus
authors.forename: Igor
authors.initials: I
authors.lastname: Sulla
authors.forename: Ladislav
authors.initials: L
authors.lastname: Mirossay
authors.forename: Marek
authors.initials: M
authors.lastname: Sarissky
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D011237:Predictive Value of Tests; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor