Postatrophic hyperplasia of the prostate gland - Neoplastic precursor or innocent bystander?

Postatrophic hyperplasia (PAH) of the prostate gland often demonstrates ove rlapping histological features with prostatic adenocarcinoma (PCA). These f eatures include small acinar growth and enlarged nuclei with prominent nucl eoli. Recent work has demonstrated that PAH is a proliferative, noninvoluti ng lesion. PAH is also histologically distinct from simple atrophy (SA), wh ich has intermediate- to large-sized glands, minimal cytoplasm, and inconsp icuous nuclei. However, despite overlapping features between PAH and PCA, h igh-grade prostatic intraepithelial neoplasm (HGPIN) is still considered th e only direct neoplastic precursor to PCA. HGPIN resembles PCA in its topog raphic distribution, cytological appearance, and molecular alterations incl uding chromosome 8p loss and chromosome 8 centromeric gain. To examine the hypothesis that PAH is the earliest histologically distinct precursor to HG PIN or PCA, the frequency, distribution, proliferative state, and chromosom e 8 gain of benign prostate, SA, PAH, HGPIN, and PCA were analyzed. Forty r adical prostatectomy specimens from men with clinically localized PCA were systematically analyzed. Proliferation was determined by Ki-67 immunohistoc hemistry (MIB-1) on formalin-fixed, paraffin-embedded tissue and quantified by digital image analysis from a total of 5,510 sample areas with benign, SA, PAH, HGPIN, and PCA. A tissue microarray was constructed to evaluate 8c gain using interphase fluorescence tit situ hybridization. SA foci (n = 12 9) and PAH foci (n = 114) were identified in the 40 cases of which 74% (95 of 129) and 88% (100 of 114) were seen in the peripheral zone, respectively CP = (.006). PAH and SA were identified adjacent to PCA in 28% (32 of 114) and 14% (18 of 129) of foci examined, respectively (P = 0.007). The median number of proliferating nuclei increased significantly from benign (1.20%) , SA (2.67%), PAH (3.62%), HGPIN (6.14%), to PCA (12.00%) (P < 0.001). The median per centage of nuclei with more than three centromeric probe signals (chromosome 8c gain) for SA, HGPIN, PAH, and PCA were 2.1, 2.8, 4.0, and 6 .0%, respectively, as compared to benign prostate with 1.3% (P = 0.006) In conclusion, the present study identified a strong topographic association b etween PAH and PCA. PAH is also seen often to be closely associated with ch ronic inflammation. Proliferation of PAH is significantly greater than beni gn prostatic epithelium and SA but less than HGPIN or PCA. Gain of 8c is si gnificantly greater in PAH than benign prostate, SA, and even HGPIN. These findings demonstrate a strong association between PAH and PCA, supporting i ts role as a neoplastic precursor.