Telomerase Activity is a Prognostic Factor for Recurrence and Survival in Rectal Cancer

Valls, Cristina; Felis, C. Piñol; Espinet, Josep Maria Reñé; García, J Buenestado; Salas, Joan Viñas

doi:10.1007/s10350-006-0820-y

Cited by 27 publications

(28 citation statements)

References 28 publications

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“…Although some histopathological features have been suggested to be associated with an increased incidence of malignancy, including tumor necrosis, mitosis rate ＞3/30 HPF, capsular invasion, vascular invasion, large nests with central degeneration, a lack of hyaline globules, a high nuclear/cytoplasmic ratio, monotony of cytological pattern, and spindle cell patterns [6,17,19], none of these differences is sufficiently diagnostic. Moreover, molecular markers, including telomerase [20], inhibins, activins [21], endothelial Per-ARNT-Sim domain protein-1, vascular endothelial growth factor, endothelin receptor type B [22], and cyclooxygenase [21], have been found to be significant but unreliable and not readily applicable for distinguishing benign from malignant pheochromocytomas. Moreover, in assaying clinical parameters, we found that age, gender, symptoms, and delay in diagnosis did not correlate with the presence of either benign or malignant pheochromocytoma.…”

Section: Discussionmentioning

confidence: 99%

Predictive Characteristics of Malignant Pheochromocytoma

Park¹,

Park²,

Song³

et al. 2009

Journal of Urology

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Purpose:The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma. Materials and Methods:We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery. Results: Malignant tumors were significantly larger than benign tumors (11.1±4.0 cm vs. 6.2±3.4 cm, p＜0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 μg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p ＜0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (≤5.5 vs. ＞5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (＞2.1 vs. ≤2.1 mg/ day/cm; 94.9% vs. 70.9%, p=0.019). Conclusions: Large tumor size (＞5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (≤2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.

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Section: Discussionmentioning

confidence: 99%

Predictive Characteristics of Malignant Pheochromocytoma

Park¹,

Park²,

Song³

et al. 2009

Journal of Urology

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“…Telomerase activity could be used to predict the risk of death or recurrence Garcia-Aranda et al [44] , 2006 91 Higher rates of telomerase activity were detected in patients older than 69 years-old. Patients who had tumours with telomerase activity and high telomere length ratios had a significantly shorter disease-free survival compared with patients whose tumours showed lower telomere length ratios Bautista et al [72] , 2007 108 Patients with low TI rectal tumours showed a higher recurrence-free survival and overall survival probability. TI was an independent prognostic factor for predicting the recurrence in the first two years after surgery and for survival in rectal cancer patients Vidaurreta et al [62] , 2007 97 Lower rates of telomerase activity were detected in tumours at early stages.…”

Section: Telomerase As a Colorectal Cancer Markermentioning

confidence: 99%

“…Moreover, defects in mismatch repair genes, which have been reported in hereditary nonpolyposis colorectal carcinoma and spontaneous tumours, may facilitate cell proliferation and survival in the absence of telomerase due to activation of a recombination-dependent pathway for telomere maintenance and the accumulation of tumourpromoting mutations [69][70][71] . Bautista et al [72] determined TI to classify tumours in 2 groups: tumours with low telomerase index and tumours with high telomerase index. In 54 patients with colon cancer, they did not find a significant association between either recurrence-free survival nor overall survival and telomerase index.…”

Section: Telomerase As a Colorectal Cancer Markermentioning

confidence: 99%

“…However, these associations were found when 41 rectal cancers were evaluated (P = 0.020 and P = 0.010, respectively): patients with tumours with low telomerase index showed a higher recurrence-free survival and overall survival probability. Moreover, when multivariate analysis was applied, Bautista et al [72] found that the telomerase index was an independent prognostic factor for predicting the recurrence in the first two years after surgery (95% CI: 1.09 to 10.8; P = 0.030) and for survival in rectal cancer patients (95% CI: 1.07 to 12.7; P = 0.030). This fact suggests a different behaviour for telomerase depending on its localization ( Table 2).…”

Section: Telomerase As a Colorectal Cancer Markermentioning

confidence: 99%

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Telomere function in colorectal cancer

Frías

Morán²,

Juan³

et al. 2009

WJGO

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Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.

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“…Certain proliferative somatic cells, such as colorectal crypts as well as gastric and endometrial cells, revealed telomerase activity and hTERT expression concomitantly with the presence of hTERT methylation (3, JB, unpublished data). An increase of telomerase activity was observed in samples of normal, transitional and tumor mucosa from patients with sporadic colorectal cancer (13). Since in the colon hTERT methylation was detected in normal and tumor tissues, we aimed to investigate whether a relationship exists between the level of telomerase activity and the degree of hTERT promoter methylation in colorectal tissues.…”

Section: Introductionmentioning

confidence: 99%

hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells

Valls¹,

Bougel²,

Piñol-Felis³

et al. 2011

Oncology Letters

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Abstract. Colorectal cancers exhibit a high telomerase activity, usually correlated with the hypermethylation of the promoter of its hTERT catalytic subunit. Although telomerase is not expressed in normal tissue, certain proliferative somatic cells such as intestinal crypt cells have demonstrated telomerase activity. The aim of this study was to determine whether a correlation exists between telomerase activity, levels of hTERT methylation and telomere length in tumoral and normal colorectal tissues. Tumor, transitional and normal tissues were obtained from 11 patients with a colorectal cancer. After bisulfite modification of genomic DNA, hTERT promoter methylation was analyzed by methylation-sensitive single-strand conformation analysis (MS-SSCA). Telomerase activity and telomere length were measured by a fluorescenttelomeric repeat amplification protocol assay and by Southern blotting, respectively. A significant increase of hTERT methylation and telomerase activity, and a reduction of the mean telomere length were observed in the tumor tissues compared to the transitional and normal mucosa. In the transitional and normal mucosa, telomerase activity was significantly lower than that in tumor tissues, even with high levels of hTERT methylation. Nevertheless, hTERT promoter methylation was not linearly correlated to telomerase activity. These data indicate that hTERT promoter methylation is a necessary event for hTERT expression, as is telomerase activity. However, methylation is not sufficient for hTERT activation, particularly in normal colorectal cells.

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Telomerase Activity is a Prognostic Factor for Recurrence and Survival in Rectal Cancer

Abstract: Measurement of telomerase activity has a diagnostic value in colorectal patients. In rectal cancer, telomerase index is an independent prognostic factor for disease progression. A telomerase index

Cited by 27 publications

References 28 publications

Predictive Characteristics of Malignant Pheochromocytoma

Predictive Characteristics of Malignant Pheochromocytoma

Telomere function in colorectal cancer

hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells

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