Expression of MUC4 Is Downregulated in Urothelial Carcinoma.
David Wagner, Adam Horn, Sukhwinder Kaur, Navneet Momi, Manjiri Lele, Surinder K Batra, Subodh M Lele. University of Nebraska Medical Center, Omaha
Background: MUC4, a high-molecular weight glycoprotein, has many unique domains involved in 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 non-invasive and invasive urothelial carcinoma (UC) which has not been previously published.
Design: Archival formalin-fixed paraffin-embedded tissues diagnosed as UC in-situ, non-invasive papillary UC and invasive UC from resection specimens were used for the present study to assess the expression of MUC4. Expression of MUC4 was also assessed in UC metastatic to regional lymph nodes. Cases with benign/non-neoplastic urothelium were used as controls. Representative tissue was selected by two of the authors followed by immunostaining with anti-MUC4 (monoclonal, prepared in our laboratory). The immunostained slides were scored using the H-score which is a summation of the product of staining intensity and proportion of cells staining.
Results: Expression of MUC4 was significantly higher in benign urothelium as compared to UC: non-invasive low grade papillary UC (p<0.0001), urothelial carcinoma in-situ/non-invasive high grade papillary UC (p<0.0084) and invasive high grade UC (p<0.0001). Expression of MUC4 did not correlate with presence or absence of invasion (p<0.1231), tumor grade (p<0.1124) or depth of invasion (p<0.3175). Expression of MUC4 was higher in benign urothelium as compared to metastatic UC within regional lymph nodes (p<0.0222), however, there was no significant difference in expression of MUC4 between that noted in the primary UC and the matched metastatic focus.
Conclusions: MUC4 is consistently downregulated in urothelial carcinoma and 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)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 172, Tuesday Morning