Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

Abstract

Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained.

Keywords: The Cancer Genome Atlas (TCGA); genetic alteration; histology; molecular pathological epidemiology; prostate cancer.

Figure 1. Morphology of distinct Gleason patterns (GPs)

(A) Individual, discrete, well-formed glands (GP 3). (B) Fused/cribriform glands (GP 4). (C) Individual neoplastic cells infiltrating the stroma between benign glands (GP 5). Scale bar, 100 μm.

Figure 2. Morphology and immunophenotype of metastatic prostatic cancer in a neck lymph node

Morphologically, the tumor is composed of round cells with solid growth (hematoxylin and eosin staining) (A). The tumor stained positive for NKX3-1 (B; nuclear staining), prostein (P501S) (C; granular perinuclear pattern), PSA (D), PSMA (E), and AR (F; nuclear staining). Scale bar, 100 μm.

Figure 3. Molecular subtypes of primary prostatic cancers by The Cancer Genome Atlas

Primary prostatic cancers can be classified into those with rearrangements in ETS family transcription factors (ERG, ETV1, ETV4, and FLI1) (ETS positive) and those without ETS rearrangements (ETS negative). ETS-positive prostatic cancers are classified by the specific ETS-fusion gene member involved: ERG, ETV1, ETV4, or FLI1. ETS-negative prostatic cancers are classified by mutations in SPOP, FOXA1, and IDH1.