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Critically shortened, dysfunctional telomeres may play a role in the genetic instabilities commonly found in cancer. We analyzed 30 surgical specimens of invasive breast carcinoma from women aged 34 to 91 years and estimated telomere lengths as telomere-to-centromere ratio values in the 5 different cell types comprising breast tissue in order to clarify telomere length variations within and between individuals using our tissue quantitative fluorescence in situ hybridization method. We obtained 3 novel findings. (1) In corresponding normal tissues, telomere length decreased in the order myoepithelial cells > normal-appearing fibroblasts > luminal epithelial cells, and telomere lengths were characteristic in these 3 cell types within each individual. (2) As expected, cancer cells had significantly shorter telomeres than myoepithelial cells (P < .0001) and normal-appearing fibroblasts (P = .0161), but there was no significant difference in telomere length between luminal cells and cancer cells (P = .6270). (3) Fibroblasts adjacent to cancer had longer telomeres than normal-appearing fibroblasts distant from cancer (P < .0001). This study, which represents the first reported assessment of telomere length variations in the 5 cell types comprising breast tissue within and between individuals, revealed that normal luminal epithelial cells and cancer cells had the shortest telomeres. Our new findings indicate that telomeres of background luminal cells are as short as those of cancer cells. Tissue quantitative fluorescence in situ hybridization, applicable to analysis of individual cells in tissue sections, is considered to be a powerful technique with considerable promise for studies in oncology.

We developed a novel method for evaluating telomere length in 6 cell types of noncancerous and cancerous mucosal tissues from 11 cases of gastric neoplasm using the quantitative fluorescence in situ hybridization method with telomere and centromere peptide nucleic acid probes. Our telomere length estimates were determined from the background-corrected telomere intensity divided by the background-corrected centromere intensity (telomere-to-centromere ratio). Our results indicated that telomere lengths in each of the cases studied were reduced in turn from fibroblasts to fundic gland cells, to glandular neck cells, and then to surface foveolar cells. However, the telomere lengths of intestinalized cells located among fundic glands were not always shorter than those of the other cell types, as reported previously by others. Helicobacter pylori infection was suggested to induce the telomere shortening seen in the fundic glands. Although the mean telomere lengths varied among the 8 gastric cancer cases, correlation of the telomere lengths with the Ki-67 labeling index was established after normalization with the fibroblast measurements. We conclude that our telomere-to-centromere ratio method can reliably estimate the telomere lengths of the 6 cell types in the gastric mucosa and clarifies the relationship between proliferative activity and the telomere length of cancer cells.