[789] Expression of α-Methylacyl-CoA Racemase (AMACR) in Urothelial Carcinoma In Situ (CIS): Comparative Utility with More Traditional Markers (CK20,CD44s,p53) in the Distinction of Urothelial CIS and Reactive Urothelial Atypia

Manju Aron, Daniel J Luthringer, Jesse K McKenney, Donna E Hansel, Danielle E Westfall, Rugvedita Parkh, Mahesha Vankalakunti, Sambit K Mohanty, Bonnie L Balzer, Mahul B Amin. Cedars-Sinai Medical Center, Los Angeles; Stanford School of Medicine, Stanford; Cleveland Clinic, Cleveland

Background: The distinction of nonpleomorphic and subtle forms of CIS from reactive atypia can be challenging based on morphology. Various markers including CK20, CD44s and p53 maybe used in making this distinction. AMACR is expressed in several carcinomas including breast, colon and prostate and their precursor lesions. It is known to be over expressed in a subset of high grade urothelial carcinomas, however not much is known about its expression in CIS. This study was undertaken to evaluate AMACR staining in CIS and to compare its utility with CK20, CD44s and p53 stained as an antibody cocktail (CIS-3).
Design: Forty five specimens including 7 benign ureters, and 38 bladder biopsies (17 reactive, 13 CIS, 8 CIS post therapy) were included in the study. The bladder biopsies were evaluated using the WHO/ISUP 2004 criteria. Immunohistochemistry was performed with AMACR and CIS-3 cocktail on all the 45 cases. Cytoplasmic staining for AMACR was graded as negative (absent to weak staining) and positive [moderate (diffuse granular) and strong (diffuse intense)]. p53 (brown, nuclear), CD44s (brown, membranous) and CK20 (red, cytoplasmic and membranous) was interpreted as positive. CIS-3 cocktail staining pattern was classified as: malignant (full thickness CK20+/-, full thickness p53+/- and CD44s-), reactive/benign (full thickness CK20 and p53- and CD44s+ basal to full thickness), and indeterminate (CK20 and p53+/- not full thickness and/or CD44s+).
Results: The staining pattern of AMACR and CIS-3 cocktail stain is outlined in the table.

Histopathology diagnosisAMACR positivity ( percent positive)CIS-3 cocktail malignant pattern (percent positive)
Benign (n=7)00
Reactive (n=17)00
CIS (n=13)7092
CIS post therapy (n=8)5083

Of the 13 cases of CIS, AMACR showed moderate to strong staining in 9 (70%), weak staining in 2 and absent staining in 2 cases. In comparison, the CIS-3 cocktail showed a malignant pattern in 12 cases (92%) and an indeterminate pattern in the remaining case. The CIS-3 cocktail stained 7 of the 8 post therapy CIS while AMACR stained only 4 cases.
Conclusions: AMACR has potential utility as a marker for CIS. Compared to CIS-3 cocktail, its utility is limited especially in the diagnosis of CIS in a post treatment setting. CK20, p53, CD44s in the appropriate morphologic context remain reliable companion markers for the diagnosis of CIS.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 96, Tuesday Afternoon


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