PMID- 23348902 OWN - NLM STAT- MEDLINE DCOM- 20140113 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Print) IS - 0893-3952 (Linking) VI - 26 IP - 6 DP - 2013 Jun TI - Novel dual-color immunohistochemical methods for detecting ERG-PTEN and ERG-SPINK1 status in prostate carcinoma. PG - 835-48 LID - 10.1038/modpathol.2012.234 [doi] AB - Identification of new molecular markers has led to the molecular classification of prostate cancer based on driving genetic lesions. The translation of these discoveries for clinical use necessitates the development of simple, reliable and rapid detection systems to screen patients for specific molecular aberrations. We developed two dual-color immunohistochemistry-based assays for the simultaneous assessment of ERG-PTEN and ERG-SPINK1 in prostate cancer. A total of 232 cases from 184 localized and 48 metastatic prostate cancers were evaluated for ERG-PTEN and 284 cases from 228 localized and 56 metastatic prostate cancers were evaluated for ERG-SPINK1. Of the 232 cases evaluated for ERG-PTEN, 81 (35%) ERG-positive and 77 (33%) PTEN-deleted cases were identified. Of the 81 ERG-positive cases, PTEN loss was confirmed in 35 (15%) cases by fluorescence in situ hybridization (FISH). PTEN status was concordant in 203 cases (sensitivity 90% and specificity 87%; P<0.0001) by both immunohistochemisty and FISH; however, immunohistochemisty could not distinguish between heterozygous and homozygous deletion status of PTEN. Of the 284 cases evaluated for ERG-SPINK1, 111 (39%) cases were positive for ERG. In the remaining 173 ERG-negative cases, SPINK1 was positive in 26 (9%) cases. SPINK1 expression was found to be mutually exclusive with ERG expression; however, we identified two cases, of which one showed concomitant expression of ERG and SPINK1 in the same tumor foci, and in the second case ERG and SPINK1 were seen in two independent foci of the same tumor nodule. Unlike the homogenous ERG staining in cancer tissues, heterogeneous SPINK1 staining was observed in the majority of the cases. Further studies are required to understand the molecular heterogeneity of cases with concomitant ERG-SPINK1 expression. Automated dual ERG-PTEN and ERG-SPINK1 immunohistochemisty assays are simple, reliable and portable across study sites for the simultaneous assessment of these proteins in prostate cancer. FAU - Bhalla, Ritu AU - Bhalla R AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. FAU - Kunju, Lakshmi P AU - Kunju LP FAU - Tomlins, Scott A AU - Tomlins SA FAU - Christopherson, Kelly AU - Christopherson K FAU - Cortez, Connie AU - Cortez C FAU - Carskadon, Shannon AU - Carskadon S FAU - Siddiqui, Javed AU - Siddiqui J FAU - Park, Kyung AU - Park K FAU - Mosquera, Juan Miguel AU - Mosquera JM FAU - Pestano, Gary A AU - Pestano GA FAU - Rubin, Mark A AU - Rubin MA FAU - Chinnaiyan, Arul M AU - Chinnaiyan AM FAU - Palanisamy, Nallasivam AU - Palanisamy N LA - eng GR - P50 CA69568/CA/NCI NIH HHS/United States GR - U01 CA113913/CA/NCI NIH HHS/United States GR - P50 CA069568/CA/NCI NIH HHS/United States GR - U01 CA111275/CA/NCI NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - R01 CA132874/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130125 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (Biomarkers, Tumor) RN - 0 (Carrier Proteins) RN - 0 (ERG protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (SPINK1 protein, human) RN - 0 (Trans-Activators) RN - 0 (Transcriptional Regulator ERG) RN - 50936-63-5 (Trypsin Inhibitor, Kazal Pancreatic) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Biomarkers, Tumor/*analysis/genetics MH - Carcinoma/*chemistry/secondary MH - Carrier Proteins/*analysis MH - Gene Deletion MH - Heterozygote MH - Homozygote MH - Humans MH - *Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Oncogene Proteins, Fusion/*analysis/genetics MH - PTEN Phosphohydrolase/*analysis/genetics MH - Predictive Value of Tests MH - Prostatic Neoplasms/*chemistry/genetics/pathology MH - Tissue Array Analysis MH - Trans-Activators/*analysis MH - Transcriptional Regulator ERG MH - Trypsin Inhibitor, Kazal Pancreatic PMC - PMC3672354 MID - NIHMS426248 EDAT- 2013/01/26 06:00 MHDA- 2014/01/15 06:00 PMCR- 2013/12/01 CRDT- 2013/01/26 06:00 PHST- 2013/01/26 06:00 [entrez] PHST- 2013/01/26 06:00 [pubmed] PHST- 2014/01/15 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - S0893-3952(22)03081-2 [pii] AID - 10.1038/modpathol.2012.234 [doi] PST - ppublish SO - Mod Pathol. 2013 Jun;26(6):835-48. doi: 10.1038/modpathol.2012.234. Epub 2013 Jan 25.