Occurrence of cell death (apoptosis) in prostatic intra-epithelial neoplasia

Abstract

The aim of our study was to assess the frequency and location of apoptotic bodies (ABs) in haematoxylin and eosin-stained sections of prostatic intraepithelial neoplasia (PIN) and then to compare the patterns with those in benign prostatic hyperplasia (BPH) and prostatic invasive adenocarcinoma (PAC). ABs were identified in all epithelial cell layers of the ducts, acini and tumour islands, as well as in the lumina contained in such structures. In the epithelial cell layers, ABs were found in general in the intercellular space and occasionally in the cytoplasm of epithelial cells. The frequency of ABs increased from BPH through PIN up to PAC. The proportions of ABs in PIN lesions of low grade (PINlow) and high grade (PINhigh) were greater than in BPH, the values decreasing from the nuclei in the basal position towards those in the luminal layer. In PINlow, the mean category values were 0.85% (standard error, SE, 0.311%) in the basal, 0.623% (SE 0.065%) in the intermediate and 0.474% (SE 0.138%) in the luminal position. In PINhigh, the mean category values were 1.006% (SE 0.16%) in the basal position, 0.713% (SE 0.182%) in the intermediate and 0.618% (SE 0.172%) in the luminal position. The proportions of ABs in adenocarcinoma with cribriform pattern decreased from the basal towards the luminal layer, as for PIN: 1.806% (SE 0.346%) in the basal position, 1.15% (SE 0.172%) in the intermediate and 0.886% (SE 0.137%) in the luminal position. In the solid/trabecular adenocarcinomas, the mean category value in the cell layer adjacent to the stroma was 2.154% (SE 0.203%), whereas in the other cell layers it was 2.052% (SE 0.239%). In small and large acinar adenocarcinomas, the proportions of positive nuclei were 1.022% (SE 0.1%) and 0.922% (SE 0.163%), respectively. The evaluation of the frequency and location of ABs gives accurate information on cell death in PIN in comparison with BPH and PAC.

Apoptosis and nuclear shapes in benign prostate hyperplasia and prostate adenocarcinoma: Comparison with and relation to Gleason score

“…11 The frequency of apoptotic bodies is highest in the basal cell layer in comparison with other epithelial cell layers in prostate diseases. 2,12 This was also observed in the present study. It is generally recognized that the frequency of apoptotic bodies increases from BPH through prostatic intraepithelial neoplasia (PIN) to PCA.…”

“…26 The average epithelial cell nuclear area was 25.4 mm 2 in normal prostate tissue and 30.1 mm 2 in prostate tumor tissue taken by needle biopsy in humans, but the nuclear area was reduced significantly to 20.1 and 23.8 mm 2 , respectively, 7 days after castration. 12 The mean area of cancer nuclei was 31.2 mm 2 and that of normal epithelium was 27.3 mm 2 . 25 All these nuclear sizes of cancer and normal nuclei were significantly different.…”

“…18 Apoptotic bodies in the epithelial cell layer have been observed with the following frequency: 0.264% in BPH, 0.679% in low-grade PIN, 0.749% in high-grade PIN, 1.282% in PCA with a cribriform pattern and 2.098% in PCA with a solid pattern. 12 In PCA, the number of apoptotic bodies varied with cell type, being 1.7% for solid undifferentiated carcinomas, 25.2% for small cell undifferentiated carcinomas and 5.5% for prostatic transitional cell carcinomas. 14 In accordance with results from most previous studies, the present study showed a higher frequency of apoptotic bodies in PCA than in BPH and, also, the higher the Gleason score for PCA, the higher the frequency of apoptosis.…”

“…It is generally recognized that the frequency of apoptotic bodies increases from BPH through prostatic intraepithelial neoplasia (PIN) to PCA. [12][13][14] It can be explained, in part, by the fact that increased expression of apoptosis-related genes, including transforming growth factor-b1, was associated with induced mouse PCA compared with BPH. 15 The positive correlation between the frequency of apoptotic bodies and Gleason grade can be partly explained by significant differences in the longevity of apoptotic bodies compared with mitotic bodies.…”

High-grade prostatic intraepithelial neoplasia

“…1,62,[65][66][67][68] Prostate cancer and high-grade PIN also have similar proliferative and apoptotic indices. 1,3,40,[69][70][71][72][73][74] It is often difficult with small foci in needle biopsies to separate cancer from suspicious foci (atypical small acinar proliferation suspicious for but not diagnostic of malignancy) when there is coexistent high-grade PIN; the difficulty is based on the inability to separate tangential cutting of the larger pre-existing acini of PIN (that may appear as small separate adjacent acini) from the smaller discrete acini of cancer.…”