Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.

Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour.

To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.

No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p = 0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p = 0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3).

While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.

European journal of cancer (Oxford, England : 1990). 2021 Feb 21 [Epub ahead of print]

Rebeca Lozano, Daniela C Salles, Shahneen Sandhu, Isabel M Aragón, Heather Thorne, Fernando López-Campos, José Rubio-Briones, Ana M Gutierrez-Pecharroman, Laneisha Maldonado, Tomas di Domenico, Alejandro Sanz, Juan D Prieto, Isabel García, María I Pacheco, Teresa Garcés, Casilda Llacer, Nuria Romero-Laorden, Francisco Zambrana, Pedro P López-Casas, David Lorente, Joaquin Mateo, Colin C Pritchard, Emmanuel S Antonarakis, David Olmos, Tamara L Lotan, Elena Castro

Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain; Genitourinary Cancer Translational Research Group, Instituto de Investigación Biomédica de Málaga, Spain., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, USA., Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain; Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain., Urology Department, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain; Department of Pathology, Hospital de Getafe, Getafe, Spain., Bioinformatics Unit, Spanish National Cancer Research Center, Madrid, Spain., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain., Department of Pathology, Hospital Universitarios Virgen de la Victoria Málaga, Spain., Genitourinary Cancer Translational Research Group, Instituto de Investigación Biomédica de Málaga, Spain; Medical Oncology, UGCI, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga, Spain., Medical Oncology, Hospital Universitario La Princesa, Madrid, Spain., Medical Oncology, Hospital Universitario Infanta Sofía, Madrid, Spain., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain; Medical Oncology, Hospital Provincial de Castellón, Castellón de la Plana, Spain., Prostate Cancer Traslational Research Unit, Vall'Hebron Institute of Oncology, Spain., University of Washington Medical Center, Seattle, USA., Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: ., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain; Genitourinary Cancer Translational Research Group, Instituto de Investigación Biomédica de Málaga, Spain; Medical Oncology, UGCI, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga, Spain. Electronic address: .