PMID- 16938570 OWN - NLM STAT- MEDLINE DCOM- 20061030 LR - 20161124 IS - 0165-4608 (Print) IS - 0165-4608 (Linking) VI - 169 IP - 2 DP - 2006 Sep TI - Interphase FISH analysis of PTEN in histologic sections shows genomic deletions in 68% of primary prostate cancer and 23% of high-grade prostatic intra-epithelial neoplasias. PG - 128-37 AB - Prostate cancer (CaP) is characterized by the accumulation of both genetic and epigenetic alterations that transform premalignant lesions to invasive carcinoma. However, the molecular events underlying this critical transition are poorly understood. One of the important genes that might play a role in CaP development is the PTEN gene. At the present time, there has been no systematic analysis of the incidence of genomic PTEN deletion by fluorescence in situ hybridization (FISH) in CaP and associated preneoplastic histologic lesions. This study assesses the frequency of PTEN deletion by interphase FISH analysis in CaP and prostatic intra-epithelial neoplasia (PIN). Dual-color FISH was performed using DNA probes for bands 10q23.3 (PTEN locus) and chromosome 10 centromere using 35 radical prostatectomy specimens. PTEN deletions were not found in 3/3 of stroma, 6/6 samples of benign glandular epithelium, and 12/12 samples of low-grade PIN. However, PTEN deletions were found in 3/13 (23%) of high-grade PIN and 24/35 (68%) of CaP. Concordance was observed between PTEN deletion status and the overall cellular PTEN protein expression levels, as assessed by immunohistochemistry. The high frequency of PTEN deletion observed in CaP versus precursor lesions implicates a pivotal role for PTEN haploinsufficiency in the transition from preneoplastic PIN to CaP. Moreover, this observation is an important consideration for novel therapeutic trials in CaP in which biologic efficacy is influenced by the activity level of PTEN. These findings draw attention to the usefulness of this relatively simple FISH assay for future applications in clinical laboratories. FAU - Yoshimoto, Maisa AU - Yoshimoto M AD - Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, 610 University Ave., Room 9-721, Toronto, Ontario, M5G 2M9 Canada. FAU - Cutz, Jean-Claude AU - Cutz JC FAU - Nuin, Paulo A S AU - Nuin PA FAU - Joshua, Anthony M AU - Joshua AM FAU - Bayani, Jane AU - Bayani J FAU - Evans, Andrew J AU - Evans AJ FAU - Zielenska, Maria AU - Zielenska M FAU - Squire, Jeremy A AU - Squire JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Gene Deletion MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Interphase MH - Male MH - PTEN Phosphohydrolase/*genetics MH - Prostatectomy MH - Prostatic Intraepithelial Neoplasia/*genetics MH - Prostatic Neoplasms/*genetics EDAT- 2006/08/30 09:00 MHDA- 2006/10/31 09:00 CRDT- 2006/08/30 09:00 PHST- 2006/02/21 00:00 [received] PHST- 2006/04/06 00:00 [accepted] PHST- 2006/08/30 09:00 [pubmed] PHST- 2006/10/31 09:00 [medline] PHST- 2006/08/30 09:00 [entrez] AID - S0165-4608(06)00252-4 [pii] AID - 10.1016/j.cancergencyto.2006.04.003 [doi] PST - ppublish SO - Cancer Genet Cytogenet. 2006 Sep;169(2):128-37. doi: 10.1016/j.cancergencyto.2006.04.003.