Characterization of ERG Gene Aberrations in Atypical Cribriform Lesions of the Prostate
B Han, K Suleman, AM Chinnaiyan, M Zhou, RB Shah. University of Michigan, Ann Arbor, MI; Cleveland Clinic, Cleveland, OH
Background: Atypical cribriform lesion (ACL) of prostate consists of cribriform glands filled with cytologically malignant cells with partial/complete basal cell lining. It may represent Cribriform High Grade Prostatic Intraepithelial Neoplasia (C-HGPIN) or Intraductal Carcinoma of the Prostate (IDC-P). The distinction between these two lesions on biopsy is critical as the latter is associated with high-grade invasive prostate cancer (PCa). The recognition of IDC-P relies on marked nuclear atypia (nuclear size 6x normal or larger) and/or comedonecrosis (Guo & Epstein, 2006).
Design: From radical prostatectomy specimens, 16 cases of ACL not associated with cancer (ACL-nonPCa, distance > 3 mm from the closest cancer), presumed to be isolated C-HGPIN, and 45 cases of cancer-associated ACL (ACL-PCa, distance < 3 mm from the closest cancer) were selected for assessment of ERG rearrangement by FISH. ACL-PCa were further divided into IDC-P (n=21) and ACL-PCa not fulfilling the criteria of IDC-P (n=24).
Results: ERG gene rearrangement was invariably absent (0/16, 0%) in ACL-nonPCa, whereas present in 75% (34/45) of ACL-PCa, of which 65% (22/34) were through deletion and 35% (12/34) through insertion. Interestingly, 16% (7/34) of the ACL-PCa showed duplication of ERG rearrangement in combination with deletion of 5'-ERG (Edel 2+). Of note, 100% (34/34) of the ACL-PCa showed concordance of ERG rearrangement with adjacent invasive PCa. There was no difference between IDC-P and ACL-PCa not fulfilling the IDC-P criteria regarding the prevalence of ERG gene aberration (79% vs.74%) and Edel2+ (21% vs. 15%).
Conclusions: ERG gene rearrangement was exclusively observed in ACL-PCa. There is no difference in ERG aberration between two classess of ACL-PCa: IDC-P and those which are not fulfilling IDC-P criteria, suggesting that the latter lesion may still represent intraductal spread of invasive cancer, instead of precancerous lesion. Understanding ERG aberration in ACL has important biological and diagnostic implications.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 124, Monday Morning