Glandular Atypia in a Background of Cystitis Glandularis: An Immunohistochemical and LCM Based Molecular Analysis
S Srivastava, Y Benedict, SY Chin, T Muliana, SS Omar, MS Tellez, M Teh. National University of Singapore, Singapore, Singapore; National University Hospital, Singapore, Singapore; National University of Singapore and National University Hospital, Singapore, Singapore
Background: We present an immunohistochemeical and molecular analysis of a case of cystitis glandularis (CG) with a focus of glandular atypia and mucin distension.
Design: In the resected bladder fragments, cystitis glandularis typical (CGTP) and cystitis glandularis intestinal metaplasia (CGIT) were identified together with atypical glands in the deep lamina propria. All three regions were immunostained with p53, CK7,CK20,CDX2,villin, beta catenin and EGFR. They were then microdissected and the DNA extracted. The molecular studies included TP53 LOH analysis and BAT26 and D2S123 microsatellite instability (MSI) analysis.
Results: There was moderate to strong nuclear expression for p53 for CGTP and the focus of glandular atypia but not for CGIT. This was confirmed by finding allelic imbalance (AI) in the subsequent TP53 LOH analysis. CGTP stained positively for CK7, beta catenin and EGFR but negatively for CK20, CDX2 and villin. CGIT stained for CK20,villin CDX2 and beta catenin but was negative for CK7 and EGFR. The focus of glandular atypia was positive for CK20, CDX2, villin and beta catenin but negative for EGFR. MSI analysis did not show any abnormality for BAT26 for CGTP,CGIT or the focus of glandular atypia. On the other hand, D2S123 marker revealed LOH at all the three foci K-Ras mutation analysis in codons 12 and 13 (exon 2) and EGFR FISH analysis (for polysomy or gene amplification) showed no abnormalities for all three foci.
Conclusions: We have confirmed by immunostaining that CGTP and CGIT have different immunoprofiles. The immunoprofile of glandular atypia resembles CGIT but stained positively for p53. This was confirmed by the detection of allelic imbalance in the TP53 LOH analysis. CGTP surprisingly stained for p53 and showed AI suggesting that it could also be a precursor in malignant transformation. The D2S123 marker displayed LOH at all three foci, suggesting this genetic change might be associated with early changes in the stepwise progression to adenocarcinoma.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 90, Tuesday Afternoon