title: In prostate cancer needle biopsies, detections of PTEN loss by fluorescence in situ hybridization (FISH) and by immunohistochemistry (IHC) are concordant and show consistent association with upgrading.
abstract: The prognostic value of phosphatase and tensin homolog (PTEN) loss in prostate cancer has primarily been evaluated by either fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). Previously, we found that PTEN loss by IHC was associated with increased risk of upgrading from biopsy (Gleason 3 + 3) to prostatectomy (Gleason 7+). Now, using an evaluable subset of 111 patients with adjacent biopsy sections, we analyzed the association between PTEN deletion in cancer and the odds of upgrading by a highly sensitive and specific four-color FISH assay. We also compared the concordance of PTEN loss by IHC and PTEN deletion by FISH. PTEN deletion was found in 27 % (12/45) of upgraded cases compared with 11 % (7/66) of controls (P = 0.03). Cancers with PTEN deletions were more likely to be upgraded than those without deletions (adjusting for age odds ratio = 3.40, 95 % confidence interval 1.14-10.11). With respect to concordance, of 93 biopsies with PTEN protein detected by IHC, 89 (96 %) had no PTEN deletion by FISH, and of 18 biopsies without PTEN protein by IHC, 15 had homozygous or hemizygous PTEN deletion by FISH. Only 4 biopsies of the 93 (4 %) with PTEN protein intact had PTEN deletion by FISH. When the regions of uncertainty in these biopsies were systematically studied by FISH, intra-tumoral variation of PTEN deletion was found, which could account for variation in immunoreactivity. Thus, FISH provides a different approach to determining PTEN loss when IHC is uncertain. Both FISH and IHC are concordant, showing consistent positive associations between PTEN loss and upgrading.
authors: Department of Genetics, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
authors: C G
authors: CG
authors: Picanço-Albuquerque
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: C L
authors: CL
authors: Morais
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: F L F
authors: FL
authors: Carvalho
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: S B
authors: SB
authors: Peskoe
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: J L
authors: JL
authors: Hicks
authors: Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors: O
authors: O
authors: Ludkovski
authors: Department of Genetics, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
authors: T
authors: T
authors: Vidotto
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: H
authors: H
authors: Fedor
authors: Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: E
authors: E
authors: Humphreys
authors: Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: M
authors: M
authors: Han
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: E A
authors: EA
authors: Platz
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: A M
authors: AM
authors: De Marzo
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.|Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: D M
authors: DM
authors: Berman
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: T L
authors: TL
authors: Lotan
authors: Department of Genetics, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil. jsquireinsp@gmail.com.|Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada. jsquireinsp@gmail.com.|Department of Pathology, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil. jsquireinsp@gmail.com.
authors: J A
authors: JA
authors: Squire
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Gleason upgrade; Hemizygous and homozygous genomic deletion; Prognostic biomarker assay; Tumor suppressor gene