title: ERG and PTEN status of isolated high-grade PIN occurring in cystoprostatectomy specimens without invasive prostatic adenocarcinoma.
abstract: High-grade prostatic intraepithelial neoplasia (HGPIN) is widely believed to represent a precursor to invasive prostatic adenocarcinoma. However, recent molecular studies have suggested that retrograde spread of invasive adenocarcinoma into pre-existing prostatic ducts can morphologically mimic HGPIN. Thus, previous molecular studies characterizing morphologically identified HGPIN occurring in radical prostatectomies or needle biopsies with concurrent invasive carcinoma may be partially confounded by intraductal spread of invasive tumor. To assess ERG and PTEN status in HGPIN foci likely to represent true precursor lesions in the prostate, we studied isolated HGPIN occurring without associated invasive adenocarcinoma in cystoprostatectomies performed at Johns Hopkins between 2009 and 2014. Of 344 cystoprostatectomies, 33% (115/344) contained invasive prostatic adenocarcinoma in the partially submitted prostate (10 blocks/case on average) and were excluded from the study. Of the remaining cases without sampled cancer, 32% (73/229) showed 133 separate foci of HGPIN and were immunostained for ERG and PTEN using genetically validated protocols. Of foci of HGPIN with evaluable staining, 7% (8/107) were positive for ERG. PTEN loss was not seen in any HGPIN lesion (0/88). Because these isolated HGPIN foci at cystoprostatectomy are unlikely to represent retrograde spread of invasive tumor, our study suggests that ERG rearrangement, but not PTEN loss, is present in a minority of potential neoplastic precursor lesions in the prostate.
authors.affiliation: Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Morais
authors.affiliation: Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231.
authors.forename: Liana B
authors.initials: LB
authors.lastname: Guedes
authors.affiliation: Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.affiliation: Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Baras
authors.affiliation: Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231; Urology, Johns Hopkins School of Medicine, Baltimore, MD 21231; Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21231.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231; Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21231. Electronic address: tlotan1@jhmi.edu.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lotan
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D015142:Baltimore; D014408:Biomarkers, Tumor / Q000032:analysis*; D016208:Databases, Factual; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D011468:Prostatectomy / Q000379:methods*; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D000071230:Transcriptional Regulator ERG / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: ERG; Immunohistochemistry; PTEN; Prostatic carcinoma; Prostatic intraepithelial neoplasia (PIN); Radical cystoprostatectomy