Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key role of down-regulated apoptosis in tumor progression

Abstract

The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly understood. Herein we report the kinetic pattern of PIN, both not associated (primary) and associated (secondary) with coexistent invasive carcinoma (PCa). Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and 20 of PCa were studied by MIB-1 immunostaining, in situ end-labeling (ISEL) and DNA histogram analysis, and the cell density in each case was estimated using the formula N = (n pi/4)2. Fifty high-power fields (HPF), or the complete lesion if smaller, were screened in each lesion, and both mean and standard deviation were recorded. Statistical differences were studied by means of Fisher's exact test. ISEL indices were significantly (P < 0.0001) lower in PCa (0.1 +/- 0.3) than in primary PIN (0.5 +/- 0.3), while the MIB-I indices were similar in both conditions (P = 0.56). Statistically significant differences were also detected for both MIB-1 and ISEL indices when secondary PIN (MIB-1 1.9 +/- 0.7, ISEL 3.7 +/- 3.3) was compared with primary PIN (MIB-1 2.5 +/- 2.1, ISEL 0.5 +/- 0.3) and PCa (P < 0.0001). In terms of cellularity, primary PIN (26.3 +/- 7.1) revealed scores significantly lower (P < 0.0001) than those recorded in PCa (39.0 +/- 8.8) and secondary PIN (32.9 +/- 14.3). In conclusion, early prostatic tumor is mainly defined by down-regulated apoptosis rather than by increased proliferation. Secondary PIN displays unique kinetic features suggesting an evolved stage of primary PIN.

Endonuclease G promotes cell death of non-invasive human breast cancer cells

“…However, multiple studies demonstrated an association of an invasive phenotype of breast cancer cells with suppressed apoptosis [3][4][5]. Similar inverse correlations between invasiveness and the ability to produce an apoptotic response after cell injury were described in prostate cancer [30], colon cancer [31,32], melanoma [33], hepatocellular carcinoma [34] and other types of neoplasia. In most of these studies, apoptosis was often measured by an endonuclease-mediated DNA fragmentation, such as TUNEL [31], in situ end-labeling (ISEL) [30] or a 200 bp-ladder-type DNA fragmentation assays [33].…”

Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front

“…High grade PIN is characterized by speci®c nuclear and morphologic features, such as enlargement of nuclei and partial breakage of the basal membrane. Koch et al and others have proposed that regulation of apoptosis and proliferation could lead to cell accumulation in PIN (Koch et al, 2000;Xie et al, 2000;Krajewaska et al, 1996). However, previous studies were based on immunohistochemistry and TUNEL assays applied to rat and human prostate tissue.…”

Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi

“…calculated in each pathological condition and patient as described. 23,24,32,33 The positivity threshold was experimentally established at the positive control in each staining batch. Only nuclei with staining features similar to those of their corresponding positive control were considered positive for any marker.…”

“…31,32 After routine dewaxing and hydration, the sections were incubated in 2 Â standard saline citrate (20 min at 801C) and digested with pronase (500 mg/ml, 25 min, room temperature) in a moist chamber.…”