Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification

Hum Pathol. 2014 Oct;45(10):2136-43. doi: 10.1016/j.humpath.2014.06.008. Epub 2014 Jun 26.


Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone-naive prostate cancer cases that progress to a highly aggressive variant of castrate-resistant disease, clinically referred to as "neuroendocrine" prostate cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer. Therefore, AURKA amplification is a potential prognostic biomarker that may help to identify patients with prostate cancer who are at high risk for developing castrate-resistant disease with clinical features of small cell carcinoma. Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a previous study, we found AURKA amplification in 6 cases of prostate cancer with Paneth cell-like cells. This morphologic pattern has been suggested to represent low-grade neuroendocrine differentiation (NED) with generally favorable prognosis. We sought to investigate the frequency of AURKA amplification and the histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty-five cases from 172 prostatectomies were evaluated for the presence of 18 morphologic features and AURKA amplification. Most prostate cancers with Paneth cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural invasion (72%), and nuclear stratification (76%). The frequency of AURKA amplification was 45%, present throughout the examined tumor nodule including areas without Paneth cell-like cells. When histologically similar cases with and without AURKA amplification were compared, this gene alteration was associated with larger extent of Paneth cell-like NED identified at magnification ×20 (P = .015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P = .033), ductal features (P = .02), and higher overall Gleason grade (P = .039). AURKA amplification was not associated with age, serum prostate specific antigen, or tumor stage. The high frequency of AURKA amplification (45%) in localized prostate cancer with Paneth cell-like NED and its potential prognostic significance warrant further investigation.

Keywords: AURKA amplification; MYCN amplification; Neuroendocrine differentiation; Paneth cell–like; Prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Aged
  • Aged, 80 and over
  • Aurora Kinase A / genetics*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Cell Differentiation
  • Female
  • Gene Amplification
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Paneth Cells / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*


  • Biomarkers, Tumor
  • AURKA protein, human
  • Aurora Kinase A