PMID- 26861919 OWN - NLM STAT- MEDLINE DCOM- 20170214 LR - 20220311 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 468 IP - 5 DP - 2016 May TI - 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. PG - 607-17 LID - 10.1007/s00428-016-1904-2 [doi] AB - 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. FAU - Picanco-Albuquerque, C G AU - Picanco-Albuquerque CG AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Morais, C L AU - Morais CL AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Carvalho, F L F AU - Carvalho FL AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Peskoe, S B AU - Peskoe SB AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. FAU - Hicks, J L AU - Hicks JL AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Ludkovski, O AU - Ludkovski O AD - Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada. FAU - Vidotto, T AU - Vidotto T AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Fedor, H AU - Fedor H AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Humphreys, E AU - Humphreys E AD - Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Han, M AU - Han M AD - Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Platz, E A AU - Platz EA AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. AD - Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - De Marzo, A M AU - De Marzo AM AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Berman, D M AU - Berman DM AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada. AD - Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Lotan, T L AU - Lotan TL AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Squire, J A AU - Squire JA AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. jsquireinsp@gmail.com. AD - Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada. jsquireinsp@gmail.com. AD - Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. jsquireinsp@gmail.com. LA - eng PT - Journal Article DEP - 20160209 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (Biomarkers, Tumor) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Aged MH - Biomarkers, Tumor/*analysis MH - Biopsy, Needle MH - Humans MH - Immunohistochemistry/methods MH - *In Situ Hybridization, Fluorescence/methods MH - Male MH - Middle Aged MH - PTEN Phosphohydrolase/*metabolism MH - Prostatectomy/methods MH - Prostatic Neoplasms/*chemistry/*pathology OTO - NOTNLM OT - Gleason upgrade OT - Hemizygous and homozygous genomic deletion OT - Prognostic biomarker assay OT - Tumor suppressor gene EDAT- 2016/02/11 06:00 MHDA- 2017/02/15 06:00 CRDT- 2016/02/11 06:00 PHST- 2015/08/13 00:00 [received] PHST- 2016/01/12 00:00 [accepted] PHST- 2015/12/15 00:00 [revised] PHST- 2016/02/11 06:00 [entrez] PHST- 2016/02/11 06:00 [pubmed] PHST- 2017/02/15 06:00 [medline] AID - 10.1007/s00428-016-1904-2 [pii] AID - 10.1007/s00428-016-1904-2 [doi] PST - ppublish SO - Virchows Arch. 2016 May;468(5):607-17. doi: 10.1007/s00428-016-1904-2. Epub 2016 Feb 9.