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Projects / Programmes source: ARIS

Genetic and radioisotopic methods in diagnostics and therapy of thyroid carcinoma

Research activity

Code Science Field Subfield
3.04.00  Medical sciences  Oncology   

Code Science Field
B790  Biomedical sciences  Clinical genetics 
B200  Biomedical sciences  Cytology, oncology, cancerology 
B480  Biomedical sciences  Endocrinology, secreting systems, diabetology 
B145  Biomedical sciences  Nuclear medicine, radiobiology 
Keywords
thyroid carcinoma, genetics, treatment, radioactive iodine, prognosis, papillary carcinoma, thyroglobulin, mutation of gene BRCA
Evaluation (rules)
source: COBISS
Researchers (9)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  08748  MSc Damijan Bergant  Oncology  Researcher  2008 - 2011  90 
2.  10330  PhD Nikola Bešić  Oncology  Head  2008 - 2011  474 
3.  19057  PhD Patricija Ećimović  Oncology  Researcher  2008  31 
4.  12023  PhD Marko Hočevar  Oncology  Researcher  2008 - 2011  472 
5.  08007  PhD Srdjan Novaković  Oncology  Researcher  2008 - 2011  499 
6.  21757  Andreja Antonija Schwarzbartl Pevec  Oncology  Researcher  2008 - 2011  35 
7.  29236  PhD Branka Stražišar  Medical sciences  Researcher  2008 - 2011  94 
8.  07750  PhD Matjaž Zwitter  Oncology  Researcher  2008 - 2011  386 
9.  12767  PhD Janez Žgajnar  Oncology  Researcher  2008 - 2011  354 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0302  Institute of Oncology Ljubljana  Ljubljana  5055733000  15,789 
Abstract
Thyroid carcinoma (TC) is a rare disease; therefore, several questions about genetics, diagnostics and treatment of TC remain unanswered. Our project will comprise four studies: (1) genetics of the patients with TC and other malignancies, (2) prognostic factors and treatment of patients with papillary thyroid microcarcinoma (PTMC), 3.) predictive factors of TC in follicular neoplasm (FN) and (4) efficacy of radioiodine (RAI) ablation of thyroid remnant after total thyroidectomy (TT) in patients with TC with regard to the dose of radioiodine. 1. We have observed that patients with medullary TC commonly have also colon or rectum carcinoma (CRC). Our hypothesis is that some mutations of RET-protooncogene are correlated with common occurrence of CRC and BC. All our patients with TC who have CRC or BC will be referred to genetic counseling. After signing the informed consent, the patients will undergo genetic testing of blood (DGGE and sequence analysis of DNA) for the presence of germline mutations for TC, CRC and BC. 2. The incidence of PTMC is increasing worldwide. In the literature, there are some discrepancies about prognostic factors in PTMC. The aim of our study is to find out which prognostic factors are accountable for the recurrence of PTMC in more than 200 patients treated at our Institute. Multivariate statistical analysis of disease-free interval and possible prognostic factors will be performed. 3. To our knowledge, the authors who studied the risk of carcinoma in FN didn't analyze the correlation between the concentration of Tg and the incidence of TC. Our hypothesis is that those patients with FN and higher preoperative serum Tg concentration are at greater risk of TC in comparison to those with lower Tg concentration who are at lower risk of TC. All the patients (more than 250) with FN, who were surgically treated at our Institute in the period 1988-2004, will be included in our retrospective study. Multivariate stepwise logistic regression analysis will be performed to test which are the prediction factors of malignancy and to find out if higher concentration of Tg is one of them. 4. The aim of our randomised prospective pilot phase 2 study, in which 40-50 patients will be included, is to test if in the patients with TC in an early stage, thyroid ablation is equally effective if 1.85 GBq or 3.7 GBq of RAI are applied after TT or near-TT.
Significance for science
1. The purpose of our study was to perform genetic sequence analysis of DNA in all our patients with thyroid carcinoma and carcinoma of colon, rectum or breast. The results of our study will contribute to better understanding of the mechanisms of carcinogenesis. An earlier diagnosis of CRC or BC in the relatives will enable the treatment of the disease in its earlier stage, thereby requiring the application of less agressive and less costly therapy. Our results confirm that genetic testing should be performed patients with multiple carcinomas. 2. In the literature, there are some discrepancies about prognostic factors in PTMC. Authopsy studies have shown that papillary microcarcinoma is present in about 30% of adult population. We found out that prognostic factors for tumor recurrence are tumor diameter and presence of lymph metastases. Results of our study contribute to the answer of the question how extensive the lymph nodes dissection should be in the patients with PTMC. Now we have a database about our patients, which is the background for our future research on this field. The purpose of our next study will be to find out which genes are associated with the presence of metastases in cervical lymph nodes. The genetic analysis of archival bioptic material of 40 patients will be performed in the laboratory of prof. J. Cerutti from the Federal University of Sao Paulo (Brazil). All samples (primary tumor without and with metastases paired with lymph-node metastasis and normal thyroid tissues) will be screened for BRAF gene mutation within exon 15 using direct sequencing. The association between presence of BRAF V600E gene, histological variants of PTMC or clinicopathological features will be performed using chi-square test. 3. Knowledge about predictive factors for carcinoma in patients with follicular neoplasm help in decision making about the extent of thyroidectomy. The results of our study are relevant because they will enable the patient and the surgeon to decide what is the optimal extent of surgical removal of the thyroid gland. We found out that patients with follicular neoplasm have higher risk of carcinoma if tumor was larger or if serum thyroglobulin level was larger than 300 ng/mL. On the basis of our results there will be less too excessive thyroid surgical procedures and therefore less unnecessary side effects in those patients with benign disease. Now we have collected the cytopathologic and histopathologic material of patients with FN. It enables us to start the next step of our research. We found out that 56% of TC in a FN represent a follicular variant of papillary TC. There are data in the literature that follicular variant of papillary TC can almost always be proved by immunohistochemical staining with commercially available antibodies to arginasa II (ARG2). In our study, we will dye our arcive cytological and histological slides of approximately 70 patients with FN. Our hypothesis is that only TC and not any other of the rest of FN will be stained by the ARG2 antibodies. Initially, we will check whether samples which were processed in different ways will be equally well stained by immunocytochemistry. By multivariate logistic analysis we will find out whether the staining with ARG2 antibodies will be an independent predictive factor for the TC. We will collaborate with Prof. Janete Cerutti from the Federal University of Sao Paulo (Brazil) and her laboratory. She is the author who described that ARG2 antibodies are specifically binding to follicular variant of papillary TC. It is known, that for this type of carcinoma elevated Tg concentration is not characteristic. Therefore, we expect that probably a higher Tg concentration will be present in the others patients with FN and elevated Tg will represent higher risks for TC than before. We expect that our research findings will have clear practical importance beacuse immunocytochemistry with ARG2 antibodies can be performed before an operative procedure.
Significance for the country
The results of our study will have direct impact on Slovenian society and economy. Out findings help us to treat the patients with thyroid microcarcinoma more effecientlly. Results of our study have an impact on our society because our patients with thyroid follicular neoplasm will be treated more efficientlly. Therefore the patients will have less unnencessary side effects.On the basis of our results about predictive factors in patients with follicular neoplasm for thyroid carcinoma there will be less too excessive thyroid surgical procedures and therefore less unnecessary side effects in those patients with benign disease. On the other hand, in the patients with malignant tumor, there will be less second surgical procedures (i.e. completion thyroidectomies), which will decrease the costs of the treatment. Results of our study will affect also treatment of patients with thyroid carcinoma in other countries and will help to promote our knowledge in other countries.
Most important scientific results Annual report 2008, 2009, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, 2009, final report, complete report on dLib.si
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