TY - JOUR
T1 - Thyroid carcinomas that express telomerase follow a more aggressive clinical course in children and adolescents
AU - Straight, A. M.
AU - Patel, A.
AU - Fenton, C.
AU - Dinauer, C.
AU - Tuttle, R. M.
AU - Francis, G. L.
N1 - Funding Information:
1The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or to reflect the opinion of the Uniformed Services University of the Health Sciences, the Department of the Army, or the Department of Defense. This study was approved by the Human Use Committee, Walter Reed Army Medical Center, Washington, DC and supported by a grant from the Henry M. Jackson Foundation for the Advancement of Military Medicine. Key-words: Thyroid, cancer, telomerase. Correspondence: Dr. Gary L. Francis, Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USA. E-mail: gfrancis@usuhs.mil Accepted September 17, 2001.
Funding Information:
This study received prior approval from the Human Use Committee of the Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC. The study was funded by a research grant from the Henry M. Jackson Foundation for the Advancement of Military Medicine.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - With each cell division, DNA is lost from the telomeres, limiting the number of divisions, and leading to senescence. Malignant tumors maintain immortality by expressing a specific DNA repair enzyme, telomerase, that replaces this DNA. We hypothesized that tumors which express telomerase would have the highest recurrence risk and we tested this by determining telomerase expression in 27 papillary thyroid carcinomas (PTC), 5 follicular thyroid carcinomas (FTC) and 13 benign thyroid lesions from children and adolescents. Patients were 6-21 yr of age (mean±SE=16.6±4.1 yr) and followed from 0-14.1 yr (mean±SE=4.71±3.5 yr). Original tumors were sectioned, and immunostained for telomerase. Telomerase-specific staining was determined by two independent, blind examiners and graded from absent (Grade 0) to intense (Grade 3). Telomerase was detected in a similar majority of benign (11/13, 85%) and malignant tumors (24/32, 75%). However, the intensity of telomerase expression was greater among FTC (mean±SE=2.4±0.5 relative intensity) followed by PTC (mean±SE=1.9±1.0 relative intensity) and benign tumors (mean±SE=1.8±1.0 relative intensity). Autoimmune lesions had lower telomerase expression (mean±SE=1.25±0.5 relative intensity) compared to FTC (p=0.01), PTC (p=0.06) and benign lesions (p=0.15). Among PTC, 19 (70%) expressed telomerase, and 8 (30%) did not. Direct invasion (no.=4, 21%), distant metastasis (no.=2, 10%) and recurrence (no.=7, 37%) developed exclusively in PTC that expressed telomerase (p=0.02). Disease-free survival was also shorter for PTC that expressed telomerase (p=0.06). Recurrence developed in 1/2 (50%) FTC that expressed telomerase. We conclude that childhood thyroid cancers which express telomerase have an increased risk of tissue invasion, metastasis, and recurrence.
AB - With each cell division, DNA is lost from the telomeres, limiting the number of divisions, and leading to senescence. Malignant tumors maintain immortality by expressing a specific DNA repair enzyme, telomerase, that replaces this DNA. We hypothesized that tumors which express telomerase would have the highest recurrence risk and we tested this by determining telomerase expression in 27 papillary thyroid carcinomas (PTC), 5 follicular thyroid carcinomas (FTC) and 13 benign thyroid lesions from children and adolescents. Patients were 6-21 yr of age (mean±SE=16.6±4.1 yr) and followed from 0-14.1 yr (mean±SE=4.71±3.5 yr). Original tumors were sectioned, and immunostained for telomerase. Telomerase-specific staining was determined by two independent, blind examiners and graded from absent (Grade 0) to intense (Grade 3). Telomerase was detected in a similar majority of benign (11/13, 85%) and malignant tumors (24/32, 75%). However, the intensity of telomerase expression was greater among FTC (mean±SE=2.4±0.5 relative intensity) followed by PTC (mean±SE=1.9±1.0 relative intensity) and benign tumors (mean±SE=1.8±1.0 relative intensity). Autoimmune lesions had lower telomerase expression (mean±SE=1.25±0.5 relative intensity) compared to FTC (p=0.01), PTC (p=0.06) and benign lesions (p=0.15). Among PTC, 19 (70%) expressed telomerase, and 8 (30%) did not. Direct invasion (no.=4, 21%), distant metastasis (no.=2, 10%) and recurrence (no.=7, 37%) developed exclusively in PTC that expressed telomerase (p=0.02). Disease-free survival was also shorter for PTC that expressed telomerase (p=0.06). Recurrence developed in 1/2 (50%) FTC that expressed telomerase. We conclude that childhood thyroid cancers which express telomerase have an increased risk of tissue invasion, metastasis, and recurrence.
KW - Cancer
KW - Telomerase
KW - Thyroid
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U2 - 10.1007/BF03344009
DO - 10.1007/BF03344009
M3 - Article
C2 - 12030599
AN - SCOPUS:0036228005
VL - 25
SP - 302
EP - 308
JO - Journal of Endocrinological Investigation
JF - Journal of Endocrinological Investigation
SN - 0391-4097
IS - 4
ER -