title: V-ets erythroblastosis virus E26 oncogene homolog (avian)/Trefoil factor 3/high-molecular-weight cytokeratin triple immunostain: a novel tissue-based biomarker in prostate cancer with potential clinical application.
abstract: Trefoil factor 3 (TFF3) is associated with various cancers and overexpressed in a subset of prostate cancers. Functional studies suggest that v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) down-regulates TFF3 expression in hormone-naïve prostate cancer. To characterize this inverse relationship, we developed a triple immunostain encompassing ERG, TFF3, and high-molecular-weight cytokeratin. Triple stain was performed on 96 tumors and 52 benign cases represented in tissue microarrays. Distinct ERG and TFF3 protein was expressed in 45% (43/96) and 36% (35/96) of prostate cancers, respectively. Coexpression was observed in 5% (5/96) of tumor cases, and 24% (23/96) did not express ERG or TFF3. The inverse expression of ERG and TFF3 was significant (P < .0001), with 57% (30/53) of ERG-negative tumors demonstrating TFF3 expression. Sensitivity and specificity of combined ERG and TFF3 expression in detecting prostate cancer were 76% and 96%, respectively. The feasibility of triple immunostain protocol was validated in a set of 76 needle biopsies. The application of this multiplex in situ biomarker for molecular characterization of prostate cancer and as a supplemental diagnostic and prognostic tool in prostate needle biopsies should be further explored.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Kyung
authors.initials: K
authors.lastname: Park
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D007633:Keratins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010455:Peptides / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D000071165:Trefoil Factor-3
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D010455:Peptides; C082495:TFF3 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D000071165:Trefoil Factor-3; D007633:Keratins
keywords: Biomarker; ERG; FISH; H&E; HGPIN; HMWCK; IHC; Prostate cancer; TFF3; TMA; TMPRSS2; fluorescence in situ hybridization; hematoxylin and eosin; high-grade prostatic intraepithelial neoplasia; high-molecular-weight cytokeratin; immunohistochemistry; siRNA; small interfering RNA; tissue microarray; transmembrane protease, serine 2; trefoil factor 3; v-ets erythroblastosis virus E26 oncogene homolog (avian)