CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia

Hum Pathol. 2021 Nov:117:60-67. doi: 10.1016/j.humpath.2021.07.006. Epub 2021 Jul 24.

Abstract

High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of cyclin-dependent kinase 19 (CDK19) by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole-tissue sections and compared CDK19 levels between HGPIN, PCa, and adjacent benign glands. In addition, CDK19 was compared with AMACR expression in a subset of intraductal carcinomas (IDCs) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists, we suggest CDK19 as diagnostic biomarker for HGPIN.

Keywords: Biomarker; Early prostate cancer diagnosis; High-grade prostatic intraepithelial neoplasia; Prostate biopsy; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cyclin-Dependent Kinases / analysis
  • Cyclin-Dependent Kinases / biosynthesis*
  • Humans
  • Male
  • Middle Aged
  • Prostatic Intraepithelial Neoplasia / diagnosis*
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • CDK19 protein, human
  • Cyclin-Dependent Kinases