| Although the mechanisms that drive cancer development and progression are not known, genomic instability occurs in most tumors and is correlated with shortened telomeres. Telomeres, which are lost each time a cell divides, are specialized protein-nucleic acid complexes that stabilize the ends of chromosomes. We hypothesized that genomic instability resulting from telomere shortening would facilitate the progression to a metastatic phenotype, by creating phenotypic variability. The purpose of this investigation was to determine if telomere DNA content, a proxy for telomere length, or if the levels of hTERT, the catalytic subunit of telomerase the enzyme that lengthens telomeres predicts survival or disease recurrence in breast and prostate cancer.; Patient histories and tumor tissues were obtained from the New Mexico Tumor Registry. Telomere DNA content (TC) was measured retrospectively in three study populations, comprising a total of 76 breast and 92 prostate tumors hTERT mRNA levels were determined using real-time RT-PCR.; In the first group, which consisted of 38 carefully matched breast tumors, including 19 from patients who died from or developed recurrent breast cancer, Kaplan-Meier analysis demonstrated that TC in DNA extracted from paraffin-embedded tumors was associated with 84-month survival in tumor (p = 0.032) and in tumor-associated normal tissue (p = 0.023). In the second study group, which consisted of 38 breast tumors Wilcoxon Rank Sums analysis demonstrated that TC in DNA extracted from frozen tumors (0.06) is associated with disease-free survival greater than 84 months and that the subset of tumors which express the highest levels of hTERT mRNA are also large, lymph node positive, high grade, aneuploid, and have high S-phase (p = 0.002). In the third study group, which consisted of 92 prostate tumors, Wilcoxon Rank Sums analysis also demonstrated that TC in DNA extracted from paraffin-embedded prostate tumors (p = 0.017) and tumor-associated normal tissue (p = 0.006) is associated with disease-free survival of greater than 84 months.; Collectively, these data show that hTERT mRNA levels may identify the subset of tumors with the worst prognostic markers at diagnosis and that telomere DNA content predicts clinical outcome in both breast and prostate tumor and tumor-associated normal tissues and has potential as powerful prognostic marker. |
