PTEN loss and ERG protein expression are infrequent in prostatic ductal adenocarcinomas and concurrent acinar carcinomas

Abstract

Background Prostatic ductal adenocarcinoma is an unusual and aggressive morphologic subtype of prostate cancer. PTEN gene deletion and ERG gene rearrangement are among the most common genomic changes in acinar prostate cancers. Though ductal adenocarcinoma most commonly occurs with synchronous usual-type acinar adenocarcinoma, little is known about the molecular phenotype of these mixed tumors. Methods We used genetically validated immunohistochemistry (IHC) assays to assess PTEN and ERG status in a group of 37 surgically treated ductal adenocarcinomas and 18 synchronous acinar adenocarcinomas where we have previously reported ERG gene rearrangement status by fluorescence in situ hybridization (FISH). A group of 34 stage and grade-matched pure acinar adenocarcinoma cases was studied as a control. Results ERG IHC was highly concordant with ERG FISH results, with 100% (36/36) concordance among ductal adenocarcinomas and 91% (31/34) concordance among 34 pure acinar carcinomas. Similar to previous FISH results, ERG expression by IHC was significantly less common among ductal adenocarcinomas (11% or 4/37) and their synchronous acinar tumors (6% or 1/18) compared to matched pure acinar adenocarcinoma cases (50% or 17/34; p= 0.0005 and 0.002, respectively). PTEN loss by IHC was also less common among ductal adenocarcinomas (18% or 6/34) and their synchronous acinar tumors (22% or 4/18) compared to matched pure acinar carcinomas (50% or 17/34; p = 0.01 and 0.08, respectively). As expected, PTEN loss was enriched among ERG positive compared to ERG-negative tumors in the pure acinar tumor control group (2.5-fold enrichment; p=0.04) however this was not observed among the ductal adenocarcinomas (1.5 fold enrichment; p=NS). Of ductal adenocarcinomas with an evaluable synchronous acinar component, ERG status was concordant in 94% (17/18) and PTEN status was concordant in 94% (16/17). Conclusions Based on PTEN and ERG, ductal adenocarcinomas and their concurrent acinar carcinomas may be clonally related in some cases and show important molecular differences from pure acinar carcinoma.

Diverse Immunoprofile of Ductal Adenocarcinoma of the Prostate with an Emphasis on the Prognostic Factors

“…In AAC, fusions between the androgen-regulated transmembrane protease serine 2 gene ( TMPRSS2 ) and the ERG estingly, Japanese population gene are present in approximately 40%–50% of cases, where ERG immunohistochemistry correlates well with fusion-positive cancer [24,26]. In the Korean population, the ERG-positive rate by immunohistochemistry was 24.4%, which is lower than those of Western population-based studies [23,27].…”

Ductal adenocarcinoma of the prostate: histogenesis, biology and clinicopathological features

“…It has been hypothesised that lower levels of circulating androgens may explain the low s-PSA seen in some DAC and less frequent rearrangements. 58 PTEN loss is less often seen in DAC than in acinar adenocarcinoma. Also, PTEN loss is not enriched in ERG positive DAC, while this is a frequent finding in acinar adenocarcinoma.…”

“…As PTEN and ERG status are the same in the DAC and acinar components, it is possible that the two tumour types are clonally related. 58 It has been shown that DAC may grow in an environment with low levels of sex hormones, proved by the decreased expression of SQLE, 5AR2 and aromatase. SQLE is the rate limiting enzyme of cholesterol synthesis expressed in prostate cancer cells, especially in prostate cancers of high grade.…”

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

“…TMPRSS2-ERG fusion occurs in 11% of the ductal component and in 5% of the acinar component of a mixed tumor, compared with 45%–50% of pure acinar adenocarcinomas [57, 58]. Similarly, PTEN is infrequently lost in the ductal and acinar components of mixed tumors and more often lost in pure acinar adenocarcinoma cells.…”

“…Chromosome 6q15 is frequently deleted in ductal adenocarcinoma cells, and deletions of MAP3K7 , which is harbored in this locus, are associated with early biochemical recurrence, advanced tumor stage, and high GS. MAP3K7 deletions are associated well with the TMPRSS2-ERG absence, which is more common in ductal than acinar adenocarcinomas [58, 63]. …”