Summary
Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor β (TGF-β) type II receptor (TβRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with Ml at three or more loci (RER+ phenotype). No mutations in the TβRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases.
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References
Blaydes, J. P. & Wynford-Thomas, D. (1996). Loss of responsiveness to transforming growth factor β is tightly linked to tumorigenicity in a model of thyroid tumour progression. Int J Cancer 65: 525–530.
Bongarzone, I., Pierotti, M. A., Monzini, N., Mondellini, P., Manenti, G., Donghi, R., Pilotti, S., Grieco, M., Santoro, M., Fusco, A., Vecchio, G. & Della Porta, G. (1989). High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene 4: 1457–1462.
Boyer, J. C., Umar, A., Risinger, J. I., Lipford, J. R., Kane, M., Yin, S., Barrett, J. C., Kolodner, R. D. & Kunkel, T. A. (1995). Microsatellite instability, mismatch repair deficiency and genetic defects in human cancer cell lines. Cancer Res 55: 6063–6070.
Brattain, M. G., Markowitz, S. D. & Willson, J. K. V. (1996). The type II transforming growth factor β receptor as a tumour suppressor gene. Curr Opin Oncol 8: 49–53.
Civitelli, S., Taurini, G., Cetta, F., Petracci, M., Pacchiarotti, M. C. & Civitelli, B. (1996). Papillary thyroid carcinoma in 3 siblings with familial adenomatous polyposis. Int J Colorectal Dis 11: 571–574.
Colletta, G., Cirafici, A. M. & Di Carlo, A. (1989). Dual effect of TGFβ on rat thyroid cells: inhibition of thyrotropin induced proliferation and reduction of thyroid-specific differentiation markers. Cancer Res 49: 3457–3462.
Coppa, A., Mincione, G., Lazzereschi, D., Ranieri, A., Turco, A., Lucignano, B., Scarpa, S., Ragano-Caracciolo, M. & Colletta, G. (1997). Restored expression of Transforming Growth Factor β type II receptor in k-ras-transformed thyroid cells, TGFβ-resistant, reverts their malignant phenotype. J Cell Physiol 172: 200–208.
Di Renzo, M. F., Olivero, M., Ferro, S., Prat, M., Bongarzone, I., Pilotti, S., Belfiore, A., Costantino, A., Vigneri, R. & Pierotti, M. A. (1992). Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7: 2549–2553.
Eshleman, J. R. & Markowitz, S. D. (1995). Microsatellite instability in inherited and sporadic neoplasms. Curr Opin Oncol 7: 83–89.
Eshleman, J. R. & Markowitz, S. D. (1996). Mismatch repair defects in human carcinogenesis. Hum Mol Genet 5: 1486–1494.
Fagin, J. A., Matsuo, K., Karkamar, A., Chen, D. L., Tang, S-H & Koeffler, H. P. (1993). High frequency of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91: 179–184.
Farid, N. R., Shy, Y. & Zou, M. (1994). The molecular biology of thyroid cancer. Endocr Rev 15: 202–232.
Hedigar, C., Williams, E. D. & Sobin, L. H. (1988). Histological Typing of Thyroid Tumours, Springer-Verlag: Berlin
Hemminki, A., Peltomäki, P., Leach, F. S., Sistonen, P., Pylkkanen, L., Meklin, J-P, Järvinen, H., Salovaara, R., Nyström-Lahti, M., De La Chapelle, A. & Aaltonen, L. A. (1994). Loss of wild type hMLH1 gene is a feature of hereditary nonpolyposis colorectal cancer. Nature Genet 8: 405–410.
Hermanek, P. & Sobin, L. H. (1987). TNM Classification of Malignant Tumours, UICC: Geneva
Hermann, M. A., Hay, I. D., Bartelt, D. H., Ritland, S. R., Dahl, R., Grant, C. S. & Jenkins, R. B. (1996). Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers. J Clin Invest 88: 1596–1604.
Karran, P. (1996). Microsatellite instability and DNA mismatch repair in human cancer. Semin Cancer Biol 7: 15–24.
Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Muraoka, M., Onda, A., Okumura, Y., Kishi, N., Iwama, T., Mori, T., Koike, M., Uishio, K., Chiba, M., Nomizu, S., Konishi, F., Utsunomiya, S. & Miyaki, M. (1996). Molecular nature of colon tumours in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic cancer. Gastroenterology 111: 307–317.
Lazzereschi, D., Ranieri, A., Mincione, G., Taccogna, S., Nardi, F. & Colletta, G. (1997). Human malignant thyroid tumours displayed reduced levels of TGFβ receptor type II mRNA and protein. Cancer Res 57: 2071–2076.
Lemoine, N. R., Mayall, E. S., Wyllie, F. S., Williams, E. D., Goins, M., Stringer, B. & Wynford-Thomas, D. (1989). High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene 4: 159–164.
Liaw, D., Marsh, D. J., Li, J., Dahia, P. L. M., Wang, S. I., Zheng, Z., Bose, S., Call, K. M., Tsou, H. C., Peacocke, M., Eng, C. & Parsons, R. (1997). Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature Genet 16: 64–67.
LiVolsi, V. (1990). Surgical Pathology of the Thyroid, pp. 173–212, Saunders: Philadelphia
Liu, B., Parson, R. E., Hamilton, S. R., Petersen, G. M., Lynch, H. T., Watson, P., Markowitz, S., Wilson, J. K. V., Green, J., De La Chapelle, A., Kinzler, K. W. & Vogelstein, B. (1994). hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds. Cancer Res 54: 4590–4594.
Lynch, H. T., Smyrk, T. & Lynch, J. (1997). An update of HNPCC (Lynch Syndrome). Cancer Genet Cytogenet 93: 84–99.
Markowitz, S., Wing, J., Myeroff, L., Parsons, R., Sun, L. Z., Lutterbaugh, J., Fan, R. S., Zborowska, E., Kinzler, K. W., Vogelstein, B., Brattain, M. & Willson, J. K. V. (1995). Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268: 1336–1338.
Myeroff, L. L., Parsons, R., Kim, S. J., Hedrick, L., Cho, K. R., Orth, K., Mathis, M., Kinzler, K. W., Lutterbaugh, J., Park, K., Bang, Y-J, Lee, H. Y., Park, J-G, Lynch, H., Roberts, A. B., Vogelstein, B. & Markowitz, S. D. (1995). A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res 55: 5545–5547.
Nicolaides, N. C., Papadopoulos, N., Liu, B., Wei, Y. F., Carter, K. C., Ruben, S. M., Rosen, C. A., Haseltine, W. A., Fleischmann, R. D., Fraser, C. M., Adams, M. D., Venter, C. J., Dunlop, M. G., Hamilton, S. R., Petersen, G. M., De La Chapelle, A., Vogelstein, B. & Kinzler, K. W. (1994). Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371: 75–80.
Ottini, L., Esposito, D. L., Richetta, A., Carlesimo, M., Palmirotta, R., Verì, M. C., Battista, P., Frati, L., Caramia, F. G., Calvieri, S., Cama, A. & Mariani-Costantini, R. (1995). Alterations of microsatellites in neurofibromas of von Recklinghausen’s disease. Cancer Res 55: 5677–5680.
Ottini, L., Palli, D., Falchetti, M., D’Amico, C., Amorosi, A., Saieva, C., Calzolari, A., Cimoli, F., Tatarelli, C., De Marchis, L., Masala, G., Mariani-Costantini, R. & Cama, A. (1997). Microsatellite instability in gastric cancer is associated with tumour location and family history in a high risk population from Tuscany. Cancer Res 57: 4523–4529.
Ottini, L., Falchetti, M., D’Amico, C., Amorosi, A., Saieva, C., Masala, G., Frati, L., Cama, A., Palli, D. & Mariani-Costantini, R. (1998). Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype. Oncogene 16: 2767–2772.
Parson, R., Myeroff, L. L., Liu, B., Willson, J. K. V., Markowitz, S. D., Kinzler, K. W. & Vogelstein, B. (1995). Microsatellite instability and mutation of the transforming growth factor β type II receptor gene in cancers. Cancer Res 55: 5548–5550.
Peltomäki, P., Lothe, R. A., Aaltonen, L. A., Pylkkänen, L., Nystrom-Lahti, M. N., Seruca, R., David, L., Holm, R., Ryberg, D., Haugen, A., Brøgger, A., Børresen, A-L & De La Chapelle, A. (1993). Microsatellite instability is associated with tumours that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res 53: 5853–5855.
Richetta, A., Ottini, L., Frati, L., Cama, A., Mariani-Costantini, R. & Calvieri, S. (1997). Microsatellite instability in primary and metastatic melanoma. J Invest Dermatol 109: 119–120.
Shibata, D., Navidi, W., Salovaara, R., Li, Z-H & Aaltonen, L. L. (1996). Somatic microsatellite mutations as molecular tumour clocks. Nature Med 2: 676–681.
Soares, P., dos Santos, N. R., Seruca, R., Lothe, R. A. & Sobrinho-Simões, M. (1997). Benign and malignant thyroid lesions show instability at microsatellite loci. Eur J Cancer 33: 293–296.
Souza, R. F., Appel, R., Yin, J., Wang, S., Smolinski, K. N., Abraham, J. M., Zou, T. T., Shi, Y. Q., Lei, J., Cottrell, J., Cymes, K., Biden, K., Simms, L., Legget, B., Lynch, P. M., Frazier, M., Powell, S. M., Harpaz, N., Sugimura, H., Young, J. & Meltzer, S. J. (1996). Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours. Nature Genet 14: 255–257.
Thibodeau, S. N., Bren, G. & Schaid, D. (1993). Microsatellite instability in cancer of the proximal colon. Science 260: 816–819.
Vermiglio, F., Schlumberger, M., Lazar, V., Lefreré, I. & Bressac, B. (1995). Absence of microsatellite instability in thyroid carcinomas. Eur J Cancer 31A: 128–128.
Werner, S. & Ingbar, S. H. (1991). The Thyroid-A Fundamental and Clinical Text, 6th edn. Braverman LE, Utiger RD (eds), pp. 1121–1206, JB Lippincott: Philadelphia
Wynford-Thomas, D. (1997). Origin and progression of thyroid epithelial tumours: cellular and molecular mechanisms. Horm Res 47: 145–157.
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Lazzereschi, D., Palmirotta, R., Ranieri, A. et al. Microsatellite instability in thyroid tumours and tumour-like lesions. Br J Cancer 79, 340–345 (1999). https://doi.org/10.1038/sj.bjc.6690054
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DOI: https://doi.org/10.1038/sj.bjc.6690054
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