Pathology, The Johns Hopkins Medical Institutions, 401 N Broadway, Baltimore, MD, MD 21231, United States.
Analytically validated assays to interrogate biomarker status in clinical samples are crucial for personalized medicine. PTEN is a tumor suppressor commonly inactivated in prostate cancer that has been mechanistically linked to disease aggressiveness. Though deletion of PTEN, as detected by cumbersome fluorescence in situ hybridization (FISH) spot counting assays, is associated with poor prognosis, few studies have validated immunohistochemical (IHC) assays to determine whether loss of PTEN protein is associated with unfavorable disease.
PTEN IHC was validated by employing formalin fixed and paraffin embedded isogenic human cell lines containing or lacking intact PTEN alleles. PTEN IHC was 100% sensitive and 97.8% specific for detecting genomic alterations in 58 additional cell lines. PTEN protein loss was then assessed on 376 prostate tumor samples, and PTEN FISH or high resolution SNP microarray analysis was performed on a subset of these cases.
PTEN protein loss, as assessed as a dichotomous IHC variable, was highly reproducible, correlated strongly with adverse pathologic features (e.g. Gleason score and pathological stage), detected between 75% and 86% of cases with PTEN genomic loss, and was found at times in the absence of apparent genomic loss. In a cohort of 217 high risk surgically treated patients, PTEN protein loss was associated with decreased time to metastasis.
These studies validate a simple method to interrogate PTEN status in clinical specimens and support the utility of this test in future multi-center studies, clinical trials and ultimately perhaps for routine clinical care.
Written by:
Lotan T, Gurel B, Sutcliffe S, Esopi D, Liu W, Xu J, Hicks J, Park B, Humphreys E, Partin A, Han M, Netto GJ, Isaacs WB, De Marzo AM. Are you the author?
Reference: Clin Cancer Res. 2011 Aug 30. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-11-1244
PubMed Abstract
PMID: 21878536
UroToday.com Prostate Cancer Section
