Biological and clinical significance of the intratumour heterogeneity of PTEN protein expression and the corresponding molecular abnormalities of the PTEN gene in glioblastomas

作者: Miguel A. Idoate , Jose Echeveste , Ricardo Diez-Valle , Maria Dolores Lozano , José Aristu

DOI: 10.1111/NAN.12117

关键词: PTENGeneClinical significanceMicrodissectionBiologyLoss of heterozygosityDNA methylationMethylationCancer researchImmunostaining

摘要: Aims Glioblastomas display marked phenotypic and molecular heterogeneity. The expression of the PTEN protein in glioblastomas also shows great intratumour heterogeneity, but significance this heterogeneity has so far received little attention. Methods We conducted a comparative study on paraffin frozen samples from 60 glioblastomas. Based immunostaining, were divided into positive (homogeneous staining) both negative (heterogeneous tumours. DNA was extracted manually microdissected representative areas, taken randomly same Loss heterozygosity (LOH) 10q23 hypermethylation status promoter studied, findings correlated with overall survival. Results PTEN present heterogeneously 42 cases homogeneously 18 cases. In homogeneous glioblastomas, no correlation found between LOH gene. Surprisingly, heterogeneous significantly more frequently (P < 0.001) PTEN-positive areas (81%) than PTEN-negative ones (35.7%). general, results tissue tumour. Only two methylation identified. A significant difference for survival LOH10q23 (P = 0.005) vs. tumours (P = 0.014). Conclusion The does not correlate abnormalities Interestingly, patients presenting either or have poorer prognosis.

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