Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses.
OBJECTIVE
We evaluated the biological properties of High-grade prostatic intraepithelial neoplasia (PIN) by immunohistochemistry and fluorescence in situ hybridization (FISH) analysis in relation to normal tissue and carcinoma lesions.


METHODS
Immunohistochemical staining and FISH were performed on 23 formalin-fixed radical prostatectomy specimens taken from patients with PIN. Assays were performed using MIB-1, chromogranin A (CGA) and an anti-androgen receptor antibody (AR). A centromere probe for chromosome 8 was used to test for aneuploidy.


RESULTS
The MIB-1 index of cancerous specimens (16.2 +/- 10.5%) was significantly higher than that of benign (1.9 +/- 1.6%, p < 0.0001) or PIN (4.0 +/- 4.5%, p < 0.0001) specimens. The percentage of CGA positive cells was significantly lower in normal tissue (1.2 +/- 1.8%) than in PIN (3.5 +/- 2.9%, p = 0.012) or carcinoma (5.4 +/- 4.9%, p = 0.005) lesions. Positive staining for AR was consistently observed in the nuclei of both benign and malignant epithelial cells, but positive cytoplasmic staining was also seen in PIN epithelial cells. No significant difference in FISH detected anomalies were found between PIN and carcinoma specimens.


CONCLUSIONS
Our studies concerning proliferative activity, NE differentiation and chromosomal anomalies of prostatic specimens support the hypothesis that PIN is a biologically intermediate stage in the pathogenesis of prostatic carcinoma. The cellular distribution of AR was altered in PIN cells, but the role of AR in PIN is not yet clear.
Tsuji
M
M
Department of Urology, University of Tokushima School of Medicine, Japan.
Kanda
K
K
Murakami
Y
Y
Kurokawa
Y
Y
Kanayama
H
H
Sano
T
T
Kagawa
S
S
D000368:Aged; D034961:Antigens, Nuclear; D001323:Autoantibodies / Q000032:analysis*; D014408:Biomarkers, Tumor; D002503:Centromere / Q000235:genetics; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002898:Chromosomes, Human, Pair 8; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis*; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011944:Receptors, Androgen / Q000276:immunology
D034961:Antigens, Nuclear; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D005819:Genetic Markers; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011944:Receptors, Androgen