PTEN Protein Expression Correlates With PTEN Gene Molecular Changes but not With VEGF Expression in Astrocytomas

Abstract

PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.

Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma

“…Positivity for mutant IDH1 was recorded when there was strong cytoplasmic staining [19] , for p53 and ATRX when more than 10% of the tumor revealed nuclear staining [18,20] . PTEN positivity was based on the cytoplasmic staining intensity and pattern [21] , and EGFR positivity was based on the grade of membrane and/or cytoplasm staining [22] . The MIB-1 labeling index evaluation was based on nuclear staining of the tumor cell [23] .…”

Growth suppression of human lung cancer cells and implanted tumors by adenovirus-mediated transfer of the PTEN gene

“…It plays an important role in a wide spectrum of physiological activities, such as cell differentiation, senescence, apoptosis, adhesion and migration, and it has recently captured attention from oncobiologists because of its tumor-suppressing properties [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] .…”

“…Zhang et al [20] also reported that the expressions of PTEN and VEGF were negatively correlated in hepatocarcinoma (HCC). But there were also notions that no correlation exists between the expression of PTEN and that of VEGF or the tumor angiogenesis [21,22] . The discrepancy may be derived from the fact that different tumor cells are used and the biological characteristics of the different tumor phenotypes differ greatly, which needs further investigations.…”

Practical Molecular Pathologic Diagnosis of Infiltrating Gliomas

“…69 Alternatively, PCR-based methods to identify LOH and IHC to identify loss of protein expression can be applied with significant correlations. 79 PTEN IHC is often difficult to interpret, however, and discordance with molecular assays is not uncommon, arguing against its routine use. 79,80 TP53 MUTATIONS TP53, a transcription factor and tumor suppressor gene located on chromosome 17p13, is mutated in approximately 50% of all human malignancies, leading to constitutive expression of the p53 protein.…”

“…79 PTEN IHC is often difficult to interpret, however, and discordance with molecular assays is not uncommon, arguing against its routine use. 79,80 TP53 MUTATIONS TP53, a transcription factor and tumor suppressor gene located on chromosome 17p13, is mutated in approximately 50% of all human malignancies, leading to constitutive expression of the p53 protein. 81 Recent studies from The Cancer Genome Atlas network showed alterations involving the p53 pathway in 78% of glioblastomas.…”