Protein patterns in cells collected from benign prostatic tissues and prostate carcinomas were analyzed using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Polypeptide expression was evaluated by computer-assisted image analysis (PDQUEST). Proteins expressed by prostate tumors were identified via in-gel digestion and subsequent matrix-assisted laser desorption/ionization mass spectrometry. In addition to cytoskeletal and mitochondrial proteins, a 40-kDa protein was identified as prostatic acid phosphatase (PAP). PAP expression decreased approximately twofold between benign and malignant tissue. Increased expression of heat shock protein 70 and decreased expression of tropomyosin 1 were also observed in the malignant tissue. The analysis of prostate material by two-dimensional gel electrophoresis and mass spectrometry shows that particular proteins are of interest as markers of disease.
Prostatic intraepithelial neoplasia (PIN) has been postulated to be the main precursor of invasive carcinoma of the prostate (IC). The occurrence, distribution and volumes of PIN and IC in addition to grade were studied in 54 patients who underwent total prostatectomy because of localised IC (T0d-T2 NO MO). PIN always occurred multifocally, localised generally in the peripheral zone (PZ) and was found in all cases. PIN 1 was the most common grade, PIN 3 the least. PIN 3 occurred exclusively in the PZ, in the vicinity of or intermingled with high grade IC. PIN and IC grades were usually concordant. The relative volumes of IC and PIN showed an inverse relationship, i.e. at small IC + PIN volumes PIN dominated, whereas at large IC + PIN volumes both relative and absolute PIN volumes were lower. Furthermore, with increasing PIN grade a tendency towards an increase in tumour volume, Gleason score and frequency of disruption of the basal cell layer was observed. These findings indicate progression from PIN to IC. DNA ploidy of PIN areas was determined by means of flow cytometry. Areas containing PIN 1, 2 or 3 were sampled (1 plug/ml of PIN). All foci displayed only diploid DNA profiles regardless of PIN volume and grade, even with coexistent IC displaying heterogeneous DNA patterns. Our results support the claim that low and medium grade prostatic carcinoma arises from near-diploid PIN stemlines and may progress into heterogeneous tumours containing non-diploid stemlines.
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