MUC4 Is Downregulated in Prostate Cancer Progression: Correlation with Gleason Pattern and High-Grade Intraepithelial Neoplasia
DG Wagner, N Momi, S Kaur, SK Batra, SM Lele. University of Nebraska Medical Center, Omaha, NE
Background: MUC4, a high-molecular weight glycoprotein, has many unique domains that can involve signaling pathways, tumor growth and metastasis. We have previously shown that the expression of MUC4 is significantly decreased in prostatic adenocarcinoma as compared to benign/hyperplastic foci. In this study, we examined the expression of MUC4 in various patterns (Gleason) of prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) which has not been previously published.
Design: Archival formalin-fixed paraffin-embedded tissue diagnosed as prostatic adenocarcinoma from resection specimens was utilized. The adenocarcinomas (28 pattern 3, 24 pattern 4 and 8 pattern 5) were re-reviewed, graded (Gleason) and foci of HGPIN (13) were selected by two of the authors followed by immunostaining with anti-MUC4. There were 31 benign controls selected for comparison. The immunostained slides were scored using the H-score which is a summation of the product of staining intensity and proportion of cells staining. Statistics were employed using the unpaired t-test.
Results: The expression of MUC4 was significantly higher in benign glands compared to HGPIN (p=0.0012) and prostatic adenocarcinoma (p=0.0001), including all examined Gleason patterns (3, 4 and 5). The H-score for MUC4 was significantly higher in HGPIN as compared to Gleason pattern 3 (p=0.0002) and significantly lower in Gleason pattern 4 as compared to Gleason pattern 3 (p=0.0445). There was a complete lack of MUC4 staining in Gleason pattern 5 and only rare positivity for MUC4 in Gleason pattern 4.
Conclusions: MUC4 is consistently downregulated in prostate cancer progression with an inverse relationship between expression and Gleason pattern (benign > HGPIN > Gleason pattern 3 > Gleason pattern 4 > Gleason pattern 5). Expression analysis of MUC4 may have diagnostic value in difficult cases. As a tumor modulator, it may confer a protective effect that might have therapeutic significance.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 142, Monday Morning