ASCO 2020: Association Between BRCA2 Status and Histologic Variants Intraductal and Cribriform Histology in Prostate Cancer

( Intraductal (IDC) and cribriform (CRIB) variant histologies in primary prostate cancer are often under-reported but are independent prognostic factors for poor outcomes. Intraductal histology has been associated with germline BRCA2 (gBRCA2) mutation as well as other DNA-damage repair gene alterations in small case series, which suggests that patients with this histology at prostatectomy or on biopsy should undergo germline genetic testing.

In this poster, Elena Castro, MD, PhD, and colleagues report the results of a case-control study to further explore the relationship between gBRCA2 mutations, certain other clinico-genomic characteristics, and intraductal or cribriform histology. For this work, 58 gBRCA2 mutation carriers were prospectively matched (1:2) with 116 non gBRCA2 patients by Gleason group and specimen type. Two urologic pathologists, who were blinded to gBRCA2 status, evaluated the corresponding tumor specimens for IDC or CRIB histology, and p63 immunostaining was performed for further histologic confirmation. Additionally, fluorescence in-situ hybridization (FISH) and sequencing were used to identify somatic BRCA2 alterations, PTEN deletion, and TMPRSS2-ERG rearrangements.

IDC features were identified in 36.2% of gBRCA2 patients and 50% of non-gBRCA2 carriers. CRIB patterns were present in 53.4% of gBRCA2 carriers and 43.1% of non-carriers. No statistically significant association between these histologies and gBRCA2 status was discovered. TMPRSS2-ERG rearrangements also had no significant association with these histologies. BRCA2 somatic deletion and PTEN homozygous deletion were significantly associated with gBRCA2 carriers. 


The authors utilized a multivariate analysis to confirm that bi-allelic BRCA2 alteration, and PTEN loss were independent risk factors for IDC histology, and bi-allelic BRCA2 alteration, Gleason grade, and higher PSA values were associated with CRIB patterns. 


Based on the data in this poster, the authors suggest that further studies are needed to establish the utility of germline genetic testing for BRCA2 mutation in patients with IDC or CRIB histologies in prostate cancer. 

Presented by: Elena Castro, MD, PhD, Genitourinary Cancer Translational Rsearch Group, IBIMA, Hospital Universitario Virgen de la Victoria, Malaga, Spain

Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2020 American Society of Clinical Oncology virtual annual meeting (#ASCO20), May 29th-May 31st, 2020