Identification of PCA3 (DD3) in prostatic carcinoma by in situ hybridization

Abstract

PCA3 is a specific marker of prostatic carcinoma. However, PCA3 has been detected only at RNA level and a corresponding PCA3 protein has never been identified. The aim of this study was to develop a technique capable of detecting PCA3 RNA on histology sections and to assess the cellular location of the molecule. Fortyeight formalin-fixed paraffin-embedded blocks of prostatectomy specimens were selected for PCA3 detection by in situ hybridization by both radioactive and chromogenic methods. Of the 48 sections, 28 contained prostatic adenocarcinoma and 20 had benign tissue located distant from the tumor. Using the radioactive detection method, 26 of 28 available cases (93%) of cancers presented at least focal cytoplasmic PCA3 expression. The benign glands located in proximity of the cancer presented PCA3 expression in eight (29%) cases, whereas those situated distant to the tumor showed focal expression in 2 of 20 (10%) cases only. Highgrade prostatic intraepithelial neoplasia (HGPIN) expressed PCA3 in 25 of 26 (96%) cases. With the chromogenic detection method, 22 of the 24 interpretable cases (92%) of cancers had at least focal cytoplasmic staining. Benign glands located close to neoplastic glands expressed PCA3 in 8 (33%) cases, but none of those distant to the tumor expressed the marker. HGPIN was positive in 17 of 24 (71%) cases. The sensitivity, specificity, positive predictive value and negative predictive value for the detection of cancer were 93, 79, 71 and 95% for the radioactive detective method and 92, 80, 71 and 95% for the chromogenic detection method, respectively. Our study shows that PCA3 RNA is expressed by most prostate cancers and HGPIN. Normal glands rarely express the marker, except those located in immediate proximity of neoplastic glands, suggesting the presence of precursor molecular changes.

Cancer-associated Changes in the Expression of TMPRSS2-ERG, PCA3, and SPINK1 in Histologically Benign Tissue From Cancerous vs Noncancerous Prostatectomy Specimens

“…This type of area can appear histologically normal, albeit molecular changes may still be detectable. Field effect-related observations in PCa 8,9,25,26 led us to the hypothesis that the HBP tissue of PCa patients in this study may have undergone molecular changes with regard to PCA3 and SPINK1 genes and TMPRSS2-ERG fusion events even though the histological examination defined the samples as non-neoplastic. This is further supported not only by the fact that the two cystoprostatectomy samples that presented TMPRSS2-ERG expression, were taken from prostates that in pathologic sectioning studies were found to contain incidental prostate tumor foci, but also by the higher likelihood of the HBP samples to contain detectable TMPRSS2-ERG mRNA if the matched cancerous sample was also TMPRSS2-ERG fusion-positive.…”

Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males

“…Recently, long noncoding RNA PCA3 has been described as one of the most prostate cancer specific genes (Bussemakers et al, 1999), it was prostate-specific expressed and sharp upregulated in prostate cancer (Bialkowska-Hobrzanska et al, 2006;Popa et al, 2007;Schmidt et al, 2006). To identify whether the promoter elements are responsible for the prostate cancer-specific expression of PCA3, in the prior study, we have isolated genomic DNA from peripheral blood leukocytes in PCa patients and healthy control individuals, and characterized the PCA3 promoter.…”

The Non-Coding Transcriptome of Prostate Cancer: Implications for Clinical Practice

“…DD3 , PCAT3 ), an lncRNA identified in 1999 via differential display analysis [33]. PCA3 is specifically expressed in prostate epithelial cells, and—compared with benign tissue— PCA3 is highly overexpressed in PCa and high-grade prostatic intra-epithelial neoplasia [33–35]. PCA3 is an antisense intronic lncRNA located in the tumor-suppressive protein-coding gene PRUNE2 .…”