Format

Send to

Choose Destination
Histopathology. 2019 Jan 12. doi: 10.1111/his.13806. [Epub ahead of print]

DNA Damage Repair Alterations are Frequent in Prostatic Adenocarcinomas with Focal Pleomorphic Giant Cell Features.

Author information

1
Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
2
Departments of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
3
Departments of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
4
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.

Abstract

AIMS:

Prostatic adenocarcinomas with focal pleomorphic giant cell features are a rare tumour subtype with abysmal clinical outcomes. More than one third of cases with this histology die within a year of the initial diagnosis of prostate cancer. Potential targeted therapies are desperately needed, however the molecular features of these tumours remain unknown.

MATERIALS AND METHODS:

Here, we performed next generation sequencing using a highly validated targeted panel (UW-Oncoplex) on somatic tumour DNA extracted from 8 cases of prostatic adenocarcinomas with focal pleomorphic giant cell features, including cases with and without prior treatment for prostate cancer.

RESULTS:

We find that DNA damage repair mutations are common in this rare subset of prostate tumours, with 2 of 8 having bi-allelic pathogenic mutations in homologous DNA repair genes (including BRCA2 and NBN) and 2 of 8 having bi-allelic pathogenic mutations in mismatch repair genes (including MSH2 and MLH1).

CONCLUSION:

These data are consistent with emerging data that DNA repair alterations are enriched among castration resistant prostate cancer and aggressive subsets of primary tumours. Given that these patients are potential candidates for PARP inhibitor and/or immune checkpoint blockade and have poor prognosis with standard therapy, we recommend tumour and germline DNA sequencing with or without mismatch repair protein immunohistochemistry be considered for all prostatic adenocarcinomas with focal pleomorphic giant cell features. This article is protected by copyright. All rights reserved.

KEYWORDS:

DNA damage repair; Pleomorphic giant cell adenocarcinoma; Prostatic adenocarcinoma; homologous recombination; hypermutation; microsatellite instability; mismatch repair

PMID:
30636012
DOI:
10.1111/his.13806

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center