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Laser-capture Microdissection of Human Prostatic Epithelium for RNA Analysis
Published on: November 26, 2015
Analysis of alpha-methylacyl-CoA racemase (P504S) expression in high-grade prostatic intraepithelial neoplasia
Chin-Lee Wu1, Ximing J Yang, Maria Tretiakova
1Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Abstract:
Alpha-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 immunohistochemistry 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.
Insights
Alpha-methylacyl-CoA racemase (AMACR), or P504S, is a prostate cancer marker. High-grade prostatic intraepithelial neoplasia (PIN) near cancer shows higher AMACR/P504S expression, suggesting a link between PIN and prostate cancer development.
Area of Science:
- Urology
- Oncology
- Pathology
Background:
- Alpha-methylacyl-CoA racemase (AMACR), also known as P504S, is an emerging molecular marker for prostate cancer.
- High-grade prostatic intraepithelial neoplasia (PIN) is recognized as a precursor lesion to prostate cancer.
- Previous studies have indicated AMACR/P504S expression in high-grade PIN, but detailed analysis was lacking.
Purpose of the Study:
- To investigate the expression patterns of AMACR/P504S in high-grade PIN.
- To determine the association between AMACR/P504S expression levels and proximity to prostate cancer.
- To provide further evidence linking high-grade PIN to prostatic adenocarcinoma.
Main Methods:
- Immunohistochemistry was employed to analyze AMACR/P504S expression.
- The study examined 3954 prostatic ducts and acini with high-grade PIN from 140 prostatectomy specimens.
- AMACR/P504S immunoreactivity was quantified using a scoring system (0 to +3).
Main Results:
- AMACR/P504S immunoreactivity was detected in 90.0% of high-grade PIN cases.
- However, only 41.5% of the glands involved by PIN showed positive AMACR/P504S expression.
- High-grade PIN glands adjacent to cancer (<5 mm) exhibited significantly higher AMACR/P504S-positive rates (56.0%) and intensity compared to those further away (>5 mm; 14%).
Conclusions:
- Strong AMACR/P504S positivity in high-grade PIN may indicate a closer association with cancer.
- The findings support the role of high-grade PIN as a precursor lesion to prostatic adenocarcinoma.
- AMACR/P504S expression analysis in PIN can offer valuable insights into prostate cancer progression.

