DNA Copy Number Changes in Thyroid Medullary Carcinomas Determined by Comparative Genomic Hybridization
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Background : A point mutation in the RET proto-oncogene, in medullary thyroid carcinoma (MTC) is well known, but no other genetic causes of MTC have been found. This study was performed to identify the most common DNA copy number changes in MTC by comparative genomic hybridization (CGH). Methods : Twenty-nine surgically resected MTC specimens were retrospectively selected from patients operated on between 1996 and 2004 at the Asan Medical Center. A review of the clinical data and pathological findings was performed. Congored staining and immunohistochemical stains (calcitonin, chromogranin A and CEA) were processed by tissue microarray. CGH analysis was performed. Results : The Congo-red stain was positive in only 12 cases. The immunohistochemical results were positive in 29 cases for chromogranin A, 26 cases for CEA and 25 cases for calcitonin. DNA copy number changes were found in 23 cases (79.3%). The most frequent change was a gain of 19q (65.5%); less frequent changes were gain of 22 (55.2%), 19p (51.7%), 16p (27.58%), 17q (17.24%), and loss of 4q (27.6%) and 3p (17.24%). Conclusions : DNA copy number changes of MTC were more common (79.3%) than reported in previous studies. The most frequent changes were gains in 19q, 22 and 19p.
Abstract
Background : A point mutation in the RET proto-oncogene, in medullary thyroid carcinoma (MTC) is well known, but no other genetic causes of MTC have been found. This study was performed to identify the most common DNA copy number changes in MTC by comparative genomic hybridization (CGH). Methods : Twenty-nine surgically resected MTC specimens were retrospectively selected from patients operated on between 1996 and 2004 at the Asan Medical Center. A review of the clinical data and pathological findings was performed. Congored staining and immunohistochemical stains (calcitonin, chromogranin A and CEA) were processed by tissue microarray. CGH analysis was performed. Results : The Congo-red stain was positive in only 12 cases. The immunohistochemical results were positive in 29 cases for chromogranin A, 26 cases for CEA and 25 cases for calcitonin. DNA copy number changes were found in 23 cases (79.3%). The most frequent change was a gain of 19q (65.5%); less frequent changes were gain of 22 (55.2%), 19p (51.7%), 16p (27.58%), 17q (17.24%), and loss of 4q (27.6%) and 3p (17.24%). Conclusions : DNA copy number changes of MTC were more common (79.3%) than reported in previous studies. The most frequent changes were gains in 19q, 22 and 19p.
참고문헌 (18)
- Hazard JB, "Medullary (solid) carcinoma of the thyroid: a clinicopathologic entity", J Clin Endocrinol Metab, 19, pp.152~161 (1959)
- Saad MF, "Medullary thyroid carcinoma. A study of the clinical features and prognostic factors in 161 patients", Medicine, 63, pp.319~342 (1984)
- Gharib H, "Medullary thyroid carcinoma. Clinicopathologic features and long-term follow-up of 65 patients treated during 1946 through 1970", Mayo Clin Process, 67, pp.934~940 (1992)
- Leboulleux S, "Medullary thyroid carcinoma; Review", Clin Endocrinol, 61, pp.299~310 (2004)
- Greene FL, "American Joint Committee on Cancer Staging Manual, Sixth edition", pp.77~87 (2002), Springer-Verlag New York, Inc, NY 10010
- Abeln EC, "Molecular genetic analysis of flow-sorted ovarian tumour cells: Improved detection of loss of heterozygosity", Br J Cancer, 70, pp.255~262 (1994)
- El-Rifai W, "Optimization of comparative genomic hybridization using flurochrome conjugated to dCTP and dUTP nucleotides", Lab Invest, 77, pp.699~700 (1997)
- Jee KJ, "Loss in 3p and 4p and Gain of 3q are concomitant aberrations in squamous cell carcinoma of the vulva", Mod Pathol, 14, pp.377~381 (2001)
- Hemmer S, "DNA copy number changes in thyroid carcinoma", Am J Pathol, 154, pp.1539~1547 (1999)
- Frisk T, "CGH alterations in medullary thyroid carcinomas in relation to the RET M918T mutation and clinical outcome", Int J of Oncol, 18, pp.1219~1225 (2001)
- Thiagalingam A, "RREB-1, a novel zinc protein, is involved in the differentiation response to ras in human medullary thyroid carcinomas", Mol Cell Biol, 16, pp.5335~5345 (1996)
- Ray SK, "Novel transcriptional potentiation of beta2", neuroD on the secretin gene promoter by the DNA-binding protein Finb, Mol Cell Biol, pp.2003, 23[DOI]
- Frisk T, "Expression of RET and its ligand complexes. GDNF", GFRalpha-1 and NTN, Eu J Endocrinol, pp.2001, 142[DOI]
- Durham PL, "Serotonergic repression of Mitogen-activated protein kinase control of the calcitonin gene-related peptide enhancer", Mol Endocrinol, 12, pp.1002~1009 (1998)
- Drosten M, "Role of MEN2Aderived RET in maintenance and proliferation of medullary thyroid carcinoma", J Natl Cancer Inst, 96, pp.1231~1254 (2004)
- Liu Z, "Antiproliferative effects of Src inhibition on medullary thyroid cancer", J Clin Endocrinol Metab, 89, pp.3503~3509 (2004)
- Franc B, "Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis)", Hum Pathol, 29, pp.1078~1084 (1998)
- Schmid KW, "‘‘Atypical’’ medullary thyroid carcinoma with little or no calcitonin expression", Virchows Arch, 433, pp.209~215 (1998)
