Looking for a Simplified Diagnostic Model to Identify Potentially Lethal Cases of Prostate Cancer at Initial Diagnosis: An ImGO Pilot Study

Abstract

The recurrent genetic anomalies used to classify prostate cancer (PC) into distinct molecular subtypes have limited relevance for clinical practice. In consideration of WHO 2016 histological classification, which includes the introduction of Gleason Score 4 for patients with cribriform component and the definition of intraductal carcinoma as a new entity, a retrospective pilot study was conducted to investigate, by histological review, if there were any variations of Gleason Score and the incidence of intraductal carcinoma and cribriform pattern, intended as "phenotypic" markers of potentially lethal PC, among metastatic castration-sensitive PC (mCSPC) and metastatic castration-resistant PC (mCRPC) samples. Potentially predictive factors were also assessed. Among 125 cases, a variation in the Gleason Score was reported in 26% of cases. A cribriform (36%) or intraductal (2%) pattern was reported in a higher percentage. Of them, a primary Gleason pattern 4 was reported in 80% of cases. All patients with intraductal carcinoma present a BRCA2 mutation, also found in 80% of cases with a cribriform pattern. This pilot study documented some hypothesis-generating data, as the evaluation of de novo mCSPC and mCRPC as phenotypic/biologic model to be translated in clinical practice. A cribriform pattern/intraductal carcinoma might be a marker of potentially lethal PC. The high incidence of TP53 and BRCA2 mutations in de novo mCSPC may also have a therapeutic implication.

Keywords: cribriform pattern; intraductal carcinoma; metastatic castration-resistant prostate cancer; metastatic castration-sensitive prostate cancer; phenotypic markers; prostate cancer.

Figure 1

Selected histological images of patients with cribriform or intraductal carcinoma. (A) Histological images of the most representative cases of prostate cancer with a cribriform pattern: medium and large glands with irregular contours, jagged edges, with irregularly and fissured lumen separated into compartments by cell bridges without interposed stroma. (B) Prostate cancer with cribriform pattern and neuroinvasion of a ganglion: perineural invasion defined as cancer cell invasion around and through nerves. (C) Intraductal carcinoma of the prostate: large glands, comedonecrosis characterized by intraluminal necrotic cells, significant nuclear atypia including enlargement, anisonucleosis, prominent nucleoli and preservation of basal cells around these glands. Scale bar = 200 µm.

Figure 2

Patterns of mutation in the 10 patients with exploratory NGS data. IDC-P = intraductal carcinoma of prostate.