Article Figures & Data
Figures
- Fig. 1.
Telomere length abnormalities in intraepithelial neoplasia lesions of the large intestine. Representative images of normal and adenomatous colonic epithelia stained for telomeric DNA (red, Cy3-labeled anti-telomeric DNA probe) and total DNA (blue, 4′,6-diamidino-2-phenylindole stain). The fluorescence intensity of the telomeric signals is linearly related to telomeric DNA length. A, normal colonic crypt showing robust telomere staining, comparable with surrounding stromal cells. B, transverse section of normal colonic crypts. C, H&E-stained area of adenoma adjacent to normal-appearing crypt. D, fluorescence microscope image of boxed area in C. Note decreased telomeric signals in the adenomatous epithelium. E, adjoining areas of adenomatous and normal colonic epithelia. F, high power image of adenomatous epithelium and intervening stroma.
- Fig. 2.
Telomere shortening in intraepithelial neoplasia lesions of the esophagus, oral cavity, and uterine cervix. A, dysplastic lesion from Barrett’s esophagus (as determined by adjacent H&E-stained section) displaying telomere shortening and merging with normal-appearing squamous epithelium showing robust telomere signals. B, high power image of esophageal dysplasia and normal epithelium. C, histologically normal region of oral cavity surface epithelium. D, dysplastic surface epithelium from same case as in C. Note diminished telomere signals compared with the underlying stroma. E, normal-appearing cervical epithelium. F, high-grade dysplasia from same case as in E.
- Fig. 3.
Telomere length heterogeneity in intestinal adenomas. A, H&E-stained region of adenomatous polyp. B, same region as shown in A, stained for telomeres and total DNA. Telomere length heterogeneity is clearly visible. C, low power image of adenoma showing marked regional telomere length heterogeneity (∗ indicates regions with abnormally long telomeres). D, high power image showing transition from very short telomere phenotype to very long telomere phenotype in contiguous stretch of adenomatous epithelium. E, 4′,6-diamidino-2-phenylindole-stained high-power image showing anaphase bridges in mitotic figure in region with short telomeres. F, crypt-crypt telomere length variability between normal-appearing colonic crypts. Arrow: crypt possessing significantly longer telomeres than neighboring crypts.
- Fig. 4.
Telomere length abnormalities in bladder intraepithelial neoplasia lesions. A, H&E-stained region of flat carcinoma in situ lesion (arrow indicates direction of surface). B, same region as seen in A. Telomere lengths are abnormally long in this lesion. C, high power image of carcinoma in situ lesion exhibiting highly variable telomere lengths.
- Fig. 5.
Verification of nuclear DNA accessibility to peptide nucleic acid (PNA) hybridization probe. Directly adjacent tissue sections of adenomatous polyp that exhibited heterogeneous telomere staining were probed with either telomere-specific PNA probe (A) or centromere-specific PNA probe (B). Note area (arrow) displaying weak telomere fluorescence signals in A but prominent centromeric signals in B.
Tables
- Table 1
Results of telomere length survey on IENa lesions
Telomere length assessment on 35 IEN lesions from 25 separate cases. Relative telomeric DNA lengths were assessed by visual comparison of telomere-specific hybridization probe fluorescence intensities between IEN lesions and their normal epithelial counterparts within the same tissue sections. Shaded boxes indicate the presence of cells with the given phenotype. Multiple shaded boxes within the same row indicate lesions with mixtures of cells possessing different overall telomere lengths (the type of variability is indicated under the “Heterogeneity” column).
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a IEN, intraepithelial neoplasia; CIS, carcinoma in situ; LG, low grade; HG, high grade; SIL, squamous intraepithelial neoplasia; Mod., moderate.
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- Table 2
Summary of telomere length abnormalities found to date in intraepithelial neoplasia lesions by in situ telomere length assessment
Site/intraepithelial neoplasia lesion n Any abnormalities (%) Short (%) Long (%) Mixed (long & short) (%) Reference Bladder/carcinoma in situ 11 100 73 91 64 Current study Large intestine/adenoma 5 100 100 20 20 Current study Large intestine/high-grade dysplasia 2 100 100 50 50 Current study Esophageal/dysplasia 6 100 100 0 0 Current study Oral cavity/dysplasia 8 88 88 0 0 Current study Uterine cervix/squamous intraepithelial neoplasia 3 100 100 0 0 Current study Prostate/prostatic intraepithelial neoplasia 45 96 96 0 0 34 , 35 Pancreas/pancreatic intraepithelial neoplasia 82 96 96 0 0 36 Breast/ductal carcinoma in situ 23 83 78 4 4 59 Bile duct/dysplasia 11 100 91 9 0 Footnote 4 Averages – 95% 92% 7% 5% Total number of lesions = 196
Volume 10, Issue 10
