Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer - Morphometric analysis in whole-mount sections

Subtle morphological changes and molecular alterations have been reported i n normal-appearing tissue in prostates with high-grade prostatic intraepith elial neoplasia (PIN) and prostate cancer (PCa). The severity and the distr ibution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to inve stigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the wholemount histological sections of three radical pro statectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whol e-mount section. The part of the prostate tissue between these two boundari es was then divided into twelve equal sectors or regions. The part within t he inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-g rade PIN and PCa, the former occupying larger areas than the latter (case n o. 2). Both high-grade PIN and PCa were present in the third sample, in whi ch PCa was more widely distributed than PIN (case no. 3). The lesion measur ed in each region was always the most severe, e.g., either high-grade PIN o r PCa. When neither were identifiable, then the normal-looking columnar epi thelium was analyzed. For each sector, the mean and standard deviation of t he nuclear area, maximum nuclear diameter, nuclear roundness factor, and nu cleolar area were calculated. In normal-looking columnar epithelium, the me an of the mean nuclear area of the sectors of case no. 1 was 35.19 mum(2) ( SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 mum(2) (SD 4.65) and 37.31 mum(2) (SD 4.36), respectively. The mean of the mean n uclear area of the sectors with high-grade PIN of case no. 2 was 49.85 mum( 2) (SD 8.44), whereas it was 54.26 mum(2) (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 mum(2) (SD 6.56) and 61.17 mum(2) (SD 8.13), respectiv ely. When considering the normal-looking tissue of the second and third cas e, 79% and 90%, respectively, of the regions showed nuclear area values gre ater than 34.94 mum(2) (e.g., the 50th percentile of the mean nuclear ar ea values of the regions of the first case). Sectors with normal-looking epit helium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other n uclear features showed a similar trend of value changes. This study demonst rates that the normal-looking ducts and acini from prostate harboring prene oplastic and neoplastic lesions show morphological nuclear abnormalities th at are not seen by the human eyes but that can be detected with image analy sis. Such changes may be of diagnostic importance, especially in cases wher e clinical suspicion for cancer prevails after a negative biopsy.