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Allelic losses and somatic mutations at the PTEN locus are present in aggressive brain tumors, endometrial and breast cancers and melanomas, reiterating its role as a tumor suppressor gene. Allelic losses at 10q23.3 in breast cancers have been correlated with an increased incidence of lymph node metastases, and poor histologic grade. Similarly, in gliomas, allelic losses at the PTEN locus are a significant predictor of shortened survival, while some studies have found an increased frequency of gene alterations in metastatic prostate cancers, compared to organ-confined tumors.
The recent availability of an immunohistochemical antibody for detection of PTEN protein levels in archival tissues has greatly facilitated the correlation of clinicopathologic parameters with PTEN expression. In prostate carcinoma, loss of PTEN expression has been correlated with a higher Gleason score, as well as an advanced clinical stage. PTEN gene mutations are the most frequent genetic aberration in endometrial adenocarcinomas and loss of PTEN expression occurs in nearly two-thirds of these cancers. Individual PTEN-negative glands in estrogen-exposed endometria are one of the earliest demonstrable abnormalities in endometrial carcinogenesis, and may prove to be a valuable adjunctive tool for predicting neoplastic progression in limited clinical specimens. Studies with the PTEN antibody are still in their infancy, and hopefully, future studies will validate the use of this assay in prognostication and risk straification.
Veripath OncoDiagnostics offers PTEN as part of the standard breast, endometrium and prostate cancer panels, but it can also be ordered individually. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Perren A et al. Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast. Am J Pathol 155:1253; 1999
2. McMenamin ME et al. Loss of PTEN expression in paraffin embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res 59:4291; 1999
3. Garcia JM et al. Allelic loss of the PTEN region (10q23) in breast carcinomas of poor pathophenotype. Clin Cancer Res 57:237; 1999
4. Mutter GL et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 92:924; 2000
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