Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer
Por:
Lozano R, Salles D, Sandhu S, Aragon I, Thorne H, Lopez-Campos F, Rubio-Briones J, Gutierrez-Pecharroman A, Maldonado L, di Domenico T, Sanz A, Prieto J, Garcia I, Pacheco M, Garces T, Llacer C, Romero-Laorden N, Zambrana F, Lopez-Casas P, Lorente D, Mateo J, Pritchard C, Antonarakis E, Olmos D, Lotan T, Castro E
Publicada:
1 abr 2021
Resumen:
Background: 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.
Patients and methods: 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.
Results: 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).
Conclusions: 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. (C) 2021 Elsevier Ltd. All rights reserved.
Filiaciones:
Lozano R:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Inst Invest Biomed Malaga, Genitourinary Canc Translat Res Grp, Malaga, Spain
Salles D:
Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA
Sandhu S:
Peter MacCallum Canc Ctr, Med Oncol, Melbourne, Vic, Australia
Aragon I:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Inst Invest Biomed Malaga, Genitourinary Canc Translat Res Grp, Malaga, Spain
Thorne H:
Peter MacCallum Canc Ctr, Med Oncol, Melbourne, Vic, Australia
Lopez-Campos F:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Hosp Univ Ramon y Cajal, Radiat Oncol, Madrid, Spain
Rubio-Briones J:
Fdn Inst Valenciano Oncol, Urol Dept, Valencia, Spain
Gutierrez-Pecharroman A:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Hosp Getafe, Dept Pathol, Getafe, Spain
Maldonado L:
Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA
di Domenico T:
Spanish Natl Canc Res Ctr, Bioinformat Unit, Madrid, Spain
Sanz A:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Prieto J:
Hosp Univ Virgen de la Victoria Malaga, Dept Pathol, Malaga, Spain
Garcia I:
Hosp Univ Virgen de la Victoria Malaga, Dept Pathol, Malaga, Spain
Pacheco M:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Garces T:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Inst Invest Biomed Malaga, Genitourinary Canc Translat Res Grp, Malaga, Spain
Llacer C:
Inst Invest Biomed Malaga, Genitourinary Canc Translat Res Grp, Malaga, Spain
Hosp Univ Virgen de la Victoria & Reg Malaga, UGCI, Med Oncol, Malaga, Spain
Romero-Laorden N:
Hosp Univ La Princesa, Med Oncol, Madrid, Spain
Zambrana F:
Hosp Univ Infanta Sofia, Med Oncol, Madrid, Spain
Lopez-Casas P:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Lorente D:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Hosp Prov Castellon, Med Oncol, Castellon de La Plana, Spain
Mateo J:
VallHebron Inst Oncol, Prostate Canc Traslat Res Unit, Barcelona, Spain
Pritchard C:
Univ Washington, Med Ctr, Seattle, WA 98195 USA
Antonarakis E:
Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Med Oncol, Sch Med, Baltimore, MD 21231 USA
Olmos D:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Inst Invest Biomed Malaga, Genitourinary Canc Translat Res Grp, Malaga, Spain
Lotan T:
Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA
Castro E:
Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid, Spain
Inst Invest Biomed Malaga, Genitourinary Canc Translat Res Grp, Malaga, Spain
Hosp Univ Virgen de la Victoria & Reg Malaga, UGCI, Med Oncol, Malaga, Spain
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