Telomere Shortening and Chromosomal Abnormalities in Intestinal Metaplasia of the Urinary Bladder

Abstract

Purpose: Although intestinal metaplasia is often found in association with adenocarcinoma of the urinary bladder, it is unclear whether intestinal metaplasia of the bladder is a premalignant lesion. Telomere shortening has recently been implicated in epithelial carcinogenesis. We used quantitative fluorescent in situ hybridization (FISH) to measure telomere length and UroVysion FISH to detect cytogenetic abnormalities in urinary bladder specimens with intestinal metaplasia. Experimental Design: Paraffin-embedded tissue blocks from 34 patients with intestinal metaplasia of the urinary bladder were evaluated. Twelve of the 34 patients had coexistent cystitis glandularis, and telomere length was measured in these lesions for comparison. Tissue sections were prepared and hybridized with a telomere-specific peptide nucleic acid probe. Quantitative FISH on interphase nuclei was used to assess telomere signal intensity. Additional sections were hybridized with centromeric probes for chromosomes 3, 7, and 17 and a locus-specific probe 9p21. Multicolor FISH was used to analyze for cytogenic abnormalities in the interphase nuclei of intestinal metaplasia. Results: In all 34 cases, reduced average telomere signal intensity was observed in the nuclei of intestinal metaplasia cells compared with adjacent control nuclei to produce a mean relative intensity of 48.5% (P < 0.0001). When cystitis glandularis was present, significant differences in the telomere-specific signal intensity existed between cystitis glandularis and normal cells (P = 0.0005) and between cystitis glandularis and intestinal metaplasia cells (P = 0.0015). Three of the 34 cases showed chromosomal gains in the UroVysion FISH assay. Conclusions: Our findings indicate that intestinal metaplasia in the urinary bladder is associated with significant telomere shortening relative to telomere length in adjacent normal urothelial cells. These lesions also occasionally showed cytogenetic abnormalities associated with telomere shortening. Our findings support the hypothesis that intestinal metaplasia of the urinary bladder is a precursor lesion to and could be a marker in the development of adenocarcinoma of the urinary bladder.

Distinguishing primary adenocarcinoma of the urinary bladder from secondary involvement by colorectal adenocarcinoma: extended immunohistochemical profiles emphasizing novel markers

“…Previous studies have suggested a close histogenetic and pathogenetic relationship of primary adenocarcinoma of the urinary bladder and colorectal adenocarcinoma. [22][23][24][25][26] Our finding that cadherin-17 and GATA3 expression are very similar in these two tumor types supports this relationship (Table 2). However, positive nuclear and cytoplasmic immunostaining for b-catenin was evident in 95% of (21/ 22) primary and 92% of (23/25) secondary colorectal adenocarcinoma, in contrast to positive membranous and cytoplasmic staining for b-catenin in 92% of (23/25) primary adenocarcinomas of the urinary bladder and 100% of (11/11) urothelial carcinomas with glandular differentiation (Po0.001).…”

Primary Mucinous Adenocarcinoma Of Urinary

“…Primary bladder adenocarcinoma are divided into urachal and non-urachal adenocarcinoma respectively based on their location, the later being the most common. [5] Based on morphology it is classified as follows adenocarcinoma not otherwise specified, colonic type, mucinous, signet ring cell , clear cell type, hepatoid and mixed type. [6] The prognosis depends on the stage of disease, 5 year survival of 70 -100 % in patients with tumor confined to bladder, however less than 30 % present at early stage.…”

Villous Adenoma Arising Within Intestinal Metaplasia on the Bladder Dome

“…Although the usual type of CG is considered a benign epithelium metaplasia, IM has been suggested to be a precursor in the development of adenocarcinoma [10,11]. However, other findings did not support IM's preneoplastic role [12].…”