Prostatic intra-epithelial neoplasia: Expression and location of proliferating cell nuclear antigen in epithelial, endothelial and stromal nuclei

Abstract

The expression and location of proliferating cell nuclear antigen (PCNA) immunostaining in epithelial, endothelial and stromal nuclei were assessed in prostatic intra-epithelial neoplasia (PIN). It was then compared with patterns in benign lesions and in invasive adenocarcinomas of the prostate. The PCNA-positive nuclei showed homogeneous or granular types of staining, or a mixture of both, and a gradation in the intensity of staining. Nuclei with granular and mixed patterns appeared lighter brown than those with a homogeneous pattern, which are darker and more often noted in PIN and invasive adenocarcinomas than in benign lesions. For epithelial PCNA-stained nuclei, the proportions in the two grades of PIN were greater than in benign prostatic hyperplasia (mean 3.16%, SE 0.31%) and prostatic atrophic ducts and acini (mean 0.56%, SE 0.09%), the values decreasing from the nuclei in the basal position towards those in the luminal layer. In grade 1, the category mean values were 9.51% (SE 1.14%) in the basal, 7.02% (SE 1.27%) in the intermediate and 6.02% (SE 0.90%) in the luminal position. In grade 2, the category mean values were 13.81% (SE 1.42%) in the basal position, 10.99% (SE 1.17%) in the intermediate and 7.91% (SE 1.43%) in the luminal position. In small and large acinar adenocarcinomas, the proportions of positive nuclei were 8.66% (SE 0.30%) and 9.06% (SE 0.30%), respectively. The category mean values in the cribriform adenocarcinomas were 14.40% (SE 0.61%) in the basal position, 11.84% (SE 1.30%) in the intermediate and 9.26% (SE 0.66%) in the luminal position. As in PIN, the proportions of immunostained nuclei in the adenocarcinoma with cribriform pattern decreased from the basal towards the luminal layer. In the solid/trabecular adenocarcinomas, the category mean value in the cell layer adjacent to the stroma was 17.60% (SE 2.92%), whereas in the other cell layers it was lower than that in the cells adjacent the stroma (mean 13.88%, SE 1.71%). For capillary endothelial and stromal cells, the percentages of PCNA-stained nuclei were much lower than those in the epithelial component. The lowest mean values were obtained in benign lesions, whereas the highest were in invasive adenocarcinomas, the percentages in PIN being intermediate.

Basal Cell Hyperplasia in the Peripheral Zone of the Prostate

“…The proliferation index was low, at about 1% for hyperplastic basal cells. This value is somewhat lower than the 2.7% (9) to 3.2% (27) previously reported for proliferation index of hyperplastic basal cells in two studies, but it is similar to the 1.4% figure obtained in a third study (28). In our series, hyperplastic basal cells had a significantly higher proliferation index compared with normal basal cells.…”

High-Grade Prostatic Intraepithelial Neoplasia in Dogs

“…The proliferative index and microvessel density of canine HGPIN are intermediate between benign epithelium and carcinoma. The results are similar to those reported for human HGPIN and prostate cancer [9, 10]and indicate that HGPIN is part of a morphologic continuum in the progression of prostate cancer.…”

“…Morphologic findings, including basal layer disruption [8], increased proliferative capacity [9], and increased microvessel density [10], suggest that HGPIN is an intermediate stage in the progression from benign epithelium to carcinoma. Foci of HGPIN are present in 85% of men with prostate cancer [11], and the presence of HGPIN on biopsy is a significant risk factor for subsequent carcinoma [12, 13].…”

Concomitant High-Grade Prostatic Intraepithelial Neoplasia Is Associated with Good Prognosis Factors and Oncologic Outcome after Radical Prostatectomy

“…Transition from HGPIN to prostate cancer can be observed from the morphological point of view and HGPIN has several features similar to those of prostate cancer [17]. For the genetic and molecular evidence, HGPIN and prostate cancer have both raised rates of cell proliferation and cell death [18,19] and raised rate of neovascularization [1] compared with those in normal prostate. They are also phenotypically and morphometrically similar [1] and they share common molecular and genetic alterations [20], although the basal cell layer is disrupted in HGPIN and absent in prostate cancer [21].…”