Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast.

摘要

The investigators employed an innovative, quantitative assay for telomere DNA content (TC) that was developed and characterized by the Principal Investigator to test the hypothesis that TC can be used to predict the likelihood of disease progression in women with Ductal Carcinoma in Situ (DCIS). The first step in this investigation was to determine whether TC measured in bulk DCIS tumor tissue is comparable to that measured in tumor epithelial cells that have been stripped of stromal cells and connective tissue by laser-capture microscopy. The investigators measured TC in 10 pairs of microdissected and undissected tissue. In 7 out of 10 instances, TC in the microdissected specimens was 72% to 112% of that in the undissected control (mean 85%). These initial results suggest that it will not be necessary to microdissect or otherwise fractionate DCIS specimens prior to TC analysis. They are currently confirming and extending these results in their own laboratory with their own instrumentation. The authors also have obtained 97 samples of DCIS tissue from women with 4 to 9 years of continuing followup for the subsequent retrospective study, have purified DNA, measured TC, and compared these data to TC measured in invasive breast tumors. The authors also are working with the New Mexico Tumor Registry to identify another 120 specimens of DCIS from women with a longer followup, including as many as possible who had recurrent disease. In summary, during the first year of this investigation the authors have accomplished the following: (1) demonstrated the ability to measure TC in DCIS tissue microdissected by laser-capture microscopy, (2) derived preliminary evidence that it will not be necessary to microdissect DCIS tissue in the subsequent retrospective study, and (3) begun to acquire and characterize the tissues that will constitute the retrospective study.