Correlations of telomere length, telomeraseactivity, and telomeric-repeat binding factor 1expression in colorectal carcinoma. Prognostic indications

Abstract

BACKGROUND Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.

METHODS Ninety‐one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric‐repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors.

RESULTS Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P = 0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P = 0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P = 0.04; relative risk, 6.48). Among patients with tumors classified as telomerase‐positive, telomere length ratios (the ratio of tumor tissues to normal tissues) ≤ 0.66 or TRF1 over‐expression conferred a favorable outcome (P = 0.03 and P = 0.05, respectively).

CONCLUSIONS The majority of CRC specimens in the current study displayed telomerase reactivation. However, only those tumors that displayed telomere elongation conferred a poor prognosis. Conversely, colorectal tumors that over‐expressed TRF1 demonstrated telomere shortening, and patients with those tumors had a better clinical course. Cancer 2006. © 2005 American Cancer Society.