Prediction of minute prostatic cancer development by telomere length measured with tissue section FISH method.

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We invited Dr. Steven Poon from the BC Cancer Center, Canada, twice in 2005 and 2006, to work as a member of our research team. In collaboration with Dr. Poon, we devised a new software program, "Tissue Telo version 2", for measurement of telomere length using tissue sections. With this approach, and the use of fluorescence in situ hybridization (FISH) with a telomere-specific probe on tissue sections, we were able to measure telomere length in archival sections of prostatic tissue, and obtained the following data :1.Difficulties with analysis of prostatic tissueProstatic tissue contains rough muscle and collagen fibers, which have very strong autofluorescence. This autofluorescence prevented us from measuring telomere length in epithelium and stroma. Although several methods for removing this autofluorescence were tried, sufficiently satisfactory fluorescence microscopy images could not be obtained. Thus it is more difficult to obtain good images using prostate than with gastrointestinal tissue.2.Improvement of quantitative fluorescence in situ hybridizationWe used centromere fluorescence intensity as an internal control, and expressed telomere length as the telomere/centromere intensity ratio (TCR). Moreover, we used TCR of cell block sections of TIG-1 to obtain more precise data. The normalized TCR was the TCR of a histologic section divided by the TCR of a section of TIG-1 from a cell block.3.TCRs of carcinoma cells were 71-83% those of normal fibroblasts. On the basis of these different TCRs, it appeared feasible to distinguish cancer cells from fibroblasts.4.TCRs of (luminal cells) were smaller than those of (basal cells) in the prostate gland. It is suggested that luminal and basal cells constitute different populations in the prostate.5.TCRs of normal fibroblasts were different from those of cancer fibroblasts. It is suggested that these cell populations in the stroma are different.