Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma

Telomere shortening leads to genomic instability and has been correlated wi th poor outcome in several types of cancer. A recently described, robust ti tration assay was used to quantify telomere DNA content in frozen and paraf fin-embedded specimens of 49 invasive human breast carcinomas, including tu mors with normal or abnormal contents of genomic DNA, which produced region al, distant, or local disease. Telomere DNA contents ranged from 53% to 370 % of the content in a reference DNA purified from normal placenta. Tumors w ere divided into three groups of approximately equal size based on increasi ng telomere DNA content. All of 16 tumors in the group with the least telom ere DNA (Group I), were aneuploid compared to 9/17 tumors in the group with the most telomere DNA (Group III). The Chi-square test for trend indicated that tumors with the least telomere DNA were significantly more likely to be aneuploid than tumors with the most telomere DNA (p < 0.002). Twelve of 14 tumors in Group I also produced metastatic disease compared to 8/15 tumo rs in Group III. The Fischer Exact Test indicated that tumors with the leas t telomere DNA were significantly more likely to be metastatic than tumors with the most telomere DNA (p < 0.05). There was no association between tel omere DNA content and patients' age, tumors' size, grade, stage, or fractio n of cells in S-phase. The correlation of reduced telomere DNA content with aneuploidy and metastasis, both of which are associated with poor outcome in invasive breast carcinoma, implies that telomere DNA content also could have prognostic value.