Ductal carcinomas of the prostate: a clinicopathological and immunohistochemical study

Abstract

Objectives To confirm the expression of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in ductal carcinomas of the prostate, and to analyse p53, Ki67, oestrogen (ER) and androgen (AR) receptors in these tumours. Materials and methods Paraffin‐embedded samples from 12 patients with ductal carcinoma of the prostate were assessed for pattern, mitotic count and the presence of a microacinar carcinoma component. There were six pure ductal and six mixed microacinar and ductal carcinomas. Sections were stained immunohistochemically for the expression of PSA, PAP, Ki67, p53, AR and ER. Clinical data were obtained from case notes. Results Six of the ductal tumours had a papillary pattern whilst the others had a cribriform appearance. The mitotic rates in the ductal areas were high in the tumours from eight of the 12 patients. PSA and PAP immunohistochemistry were positive in all the cases. No ER immunoreactivity was found in any of the patients. Ten of the ductal tumours showed strong reactivity with AR, the other two were weakly positive; two of the tumours were strongly positive for p53 protein. All the ductal carcinomas expressed Ki67, three having >25% nuclear marking. One patient who was strongly positive for p53 and had a high Ki67 score survived only one year after diagnosis. Survival ranged from 1 to 13 years after diagnosis. Conclusion This study confirms the expression of PSA and PAP in ductal carcinomas of the prostate. The percentage of tumours expressing p53 was similar to that published for high‐grade microacinar carcinomas. The results for Ki67 suggest that ductal tumours have higher scores than microacinar tumours, but further studies are required to ascertain if this is significantly different. As half the patients with ductal tumours had co‐existent microacinar tumours, we advise transrectal prostatic biopsies in patients diagnosed with pure ductal carcinomas on transurethral resection specimens, to exclude high‐grade microacinar carcinomas. The presence of AR and the lack of ER in all the ductal carcinomas confirms that these tumours are prostatic in origin and should be treated with anti‐androgen therapy.

Gene expression profiles of ductal versus acinar adenocarcinoma of the prostate

“…25 In a small series, ductal adenocarcinomas displayed more frequent cytokeratin 20 expression. 16 Immunohistochemical staining for other proteins, including estrogen receptor, androgen receptor, p53, bcl-2, and CEA, has been performed in a few ductal adenocarcinoma cases, 7,14,18,19,30 but it is not established whether there is a difference in expression compared with acinar adenocarcinoma. Genes identified as exhibiting a greater than twofold change in ductal versus acinar adenocarcinoma are potential candidates for further study in attempts to explain the different histopathological features and disparate clinical behavior of ductal adenocarcinoma of the prostate.…”

“…Limited scale data do exist on comparative protein expression in ductal versus acinar adenocarcinoma, 7,12,[14][15][16][17][18][19][20][21][22][23][24][25] but comparative global gene expression profiling has not been performed. The aim of this study was to examine the gene expression profiles of ductal versus acinar adenocarcinoma to assess the molecular relatedness of ductal and acinar adenocarcinomas and to identify potential molecular differences that may explain the different histopathological features and disparate clinical behavior of ductal adenocarcinoma of the prostate.…”

Unusual subtypes of prostate cancer

“…[4][5][6][7][8][9][10][11][12] It can be identified as a lesser pattern in up to 3% of cases. Initially, these tumors were believed to be of endometrial origin arising in the verumontanum, a mü llerian remnant; 4,5 however, it is now recognized that these are of prostatic epithelial origin.…”

“…Initially, these tumors were believed to be of endometrial origin arising in the verumontanum, a mü llerian remnant; 4,5 however, it is now recognized that these are of prostatic epithelial origin. [6][7][8][9][10][11][12] The concept of ductal adenocarcinoma as a specific entity has been challenged, most recently by Bock and Bostwick. 13 In a study utilizing LOH analysis of 12 polymorphic microsatellite markers, frequently lost in prostate cancer, Dawkins et al 14 reported LOH in none of the Gleason grade 3 tumors studied, 9% of high-grade prostatic intraepithelial neoplasia (HGPIN) lesions, 29% of Gleason grade 4 cancers and 60% of ductal adenocarcinomas, suggesting that these are in fact a different lesion.…”

Computational Modeling and Experimental Evaluation of a Novel Prodrug for Targeting the Extracellular Space of Prostate Tumors

“…One of the targets on the list obtained by this combined data-mining approach is human prostatic acid phosphatase (PAP). This hydrolase was selected because it is a phosphatase that is expressed and secreted exclusively by the prostate and overexpressed and abundantly secreted by prostate cancer cells (8)(9)(10). Consequently, serum levels of PAP are frequently elevated in patients and are used as a marker for the disease (11)(12)(13)(14)(15).…”