Elsevier

Human Pathology

Volume 35, Issue 8, August 2004, Pages 1008-1013
Human Pathology

Original contributions
Analysis of α-methylacyl-CoA racemase (P504S) expression in high-grade prostatic intraepithelial neoplasia

https://doi.org/10.1016/j.humpath.2004.03.019Get rights and content

Abstract

α-methylacyl-CoA racemase (AMACR), also known as P504S, is a recently identified molecular marker for prostate cancer. The expression of AMACR/P504S has also been observed in high-grade prostatic intraepithelial neoplasia (PIN), a precursor lesion of prostate cancer. However, a detailed study focusing on the analysis of AMACR/P504S expression in high-grade PIN has not been performed. In this study, we analyzed AMACR/P504S expression by immunohistochemisty in 3954 prostatic ducts and acini with high-grade PIN from 140 prostatectomy specimens. AMACR/P504S immunoreactivity was measured as negative (0), weakly positive (+1), moderately positive (+2), and strongly positive (+3). AMACR/P504S immunoreactivity was detected in 90.0% (126/140) of high-grade PIN cases, although only 41.5% (1642/3954) of prostatic glands involved by PIN showed AMACR/P504S immunoreactivity. A significantly higher AMACR/P504S-positive rate (56.0%) was found in isolated high-grade PIN glands adjacent to cancer (distance less than 5 mm) compared with those away from cancer (distance more than 5 mm; 14%, P < 0.0001). High-grade PIN glands adjacent to cancer also showed a higher (P < 0.0004) AMACR/P504S intensity (1.62) than did those away from cancer (1.11). Our results suggest that PIN strongly positive for AMACR/P504S might be more closely associated with cancer than PIN negative or weakly positive for AMACR/P504S. This study provides additional evidence to link high-grade PIN as a precursor lesion to prostatic adenocarcinoma.

Section snippets

Case selection

High-grade PIN was defined as the presence of neoplastic cells with significant nuclear atypia within preexisting prostatic glands (ducts and acini). A total of 140 cases of high-grade PIN present in prostatectomy specimens were randomly selected from 3 participating hospitals. Prostatectomies were performed for the treatment of prostatic adenocarcinoma in 130 cases (radical prostatectomy), bladder urothelial carcinoma in 5 cases (cystoprostatectomy), or benign prostatic hyperplasia in 5 cases

AMACR/P504S expression in high-grade PIN

The diagnosis of high-grade PIN was confirmed by the presence of basal cells positive for 34βE12 in all 140 cases. AMACR/P504S immunoreactivity was detected in 126 of the 140 cases (90.0%) of high-grade PIN that were included in the study (Table 2). However, not all high-grade PIN glands were positive for AMACR/P504S. Of the 3954 prostatic glands involved by high-grade PIN in these 140 cases, 1642 glands (41.5%) were positive for AMACR/P504S. Furthermore, high-grade PIN had weaker staining

Discussion

In recent years, there has been an increasing interest in identifying precursor lesions of prostate cancer. The most promising candidate to date is high-grade PIN. The original observation suggesting this association was made by McNeal and Bostwick2 in prostates in which a high percentage of PIN co-existed with prostatic adenocarcinoma. Since then, additional supporting biological and biochemical evidence has been obtained.13, 14, 15, 16, 17 Pathological diagnosis of high-grade PIN is

Acknowledgements

The authors thank Dr Borko Jovanovich, Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine for statistical analysis.

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