Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia.
BACKGROUND
Benign prostatic hyperplasia (BPH) is a slowly progressive abnormal glandular enlargement with heterogeneous morphology. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in this common and significantly morbid disease.


METHODS
Prostatic tissue from 20 patients with BPH and no prior or subsequent prostatic carcinoma was obtained by transurethral prostatectomy (TURP) at the University of California Davis. Apoptotic regulatory proteins: BCL2, BAX and p27 were analyzed by immunohistochemistry and evaluated for expression in four distinct histologic patterns: hyperplastic epithelium, nodules, dilated glands and atrophic/inflammatory glands.


RESULTS
Particularly striking was the decreased expression of BAX and an abnormal BCL2 : BAX ratio within all nodules relative to expression in other epithelial patterns. p27 expression was decreased in 35% of the hyperplastic epithelial areas and 10% of the nodules.


CONCLUSIONS
Overall, abnormal expression of BCL2, BAX and/or p27 was identified in the hyperplastic epithelium of 19 (90%) of specimens and all 12 (100%) of the hyperplastic nodules. The high frequency of abnormalities in apoptosis regulatory genes, suggests that alteration of apoptotic pathways is important for the development of this condition.
Department of Pathology, University of California Davis Health System, 4400V Street, Sacramento, CA 95817, USA. regina.gandour-edwards@ucdmc.ucdavis.edu
R
R
Gandour-Edwards
P C
PC
Mack
R W
RW
Devere-White
P H
PH
Gumerlock
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27