Gene expression profile analysis in laryngeal cancer by high-density oligonucleotide microarrays.

The assessment of gene expression profile in laryngeal cancer shall allow to implement molecular biology methods in diagnostics, as well as in prognosis of the course of disease. Thus, it may influence the choice of the most optimal decisions in regards to the method of treatment, extent of surgical procedure, or the necessity of adding post-operative radiotherapy. The aim of the project was to analyse the gene expression profile of laryngeal cancer using oligonucleotide microarrays, aiming to derive novel molecular markers for that carcinoma. The study comprised a group of 14 patients (12 males and 2 females) with squamous cell laryngeal carcinoma, diagnosed and surgically treated between 2005 - 2007 in the ENT Department of the Silesian Medical University in Katowice, Poland. RNA was isolated from frozen tissue fragments. To assess gene expression profile, high density oligonucleotide microarrays (Affymetrix U 133 Plus 2.0) were applied, with over 54 thousand probesets for over 47 thousand transcripts. Four genes, previously not assesed in diagnostic context in laryngeal carcinoma, seemed to be valuable markers of that neoplasm. These are: metalloproteinase ADAM12, cycline-dependent kinase 2 - CDK2, kinesine 14 - KIF14, suppressor 1 of checkpoint - CHES1.

Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients.

PURPOSE: The study was undertaken to evaluate the frequency of inherited medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease. A stepwise algorithm was used depending on clinical indices and the age of patient at MTC diagnosis. PATIENTS AND METHODS: One hundred sixteen patients with MTC verified by postoperative pathologic examination were subjected to genetic analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain reaction, restriction endonuclease digestion, and DNA sequencing. RESULTS: Among 116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10 and 11). The frequency of inherited disease among patients younger than 45 years at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11. Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1% additional diagnoses, giving a risk of 16.3% in this age group. One previously unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and 4.5% in polymorphic variants L769L and S836S, respectively, were observed. The frequency for L769L was higher than in older patients (P <.05). CONCLUSION: The frequency of inherited disease among apparent sporadic medullary thyroid carcinoma patients is close to 10% in the Polish population of MTC patients. The extended analysis of all known RET proto-oncogene mutation sites is obligatory in patients younger than 45 years at diagnosis, but we also see the need to analyze the impact of rarer mutations in older patients.

[Possibilities and limitations of intraoperative isotope detection for thyroid carcinoma]. / Mozliwosci i ograniczenia sródoperacyjnej detekcji izotopowej raka tarczycy.

Intraoperative probes become increasingly important in the surgical management of cancer. Attempts with gamma probe guided surgery to improve the completeness of surgical excision of radioiodine avid tissues in thyroid cancer have been performed through several decades. The first Polish results by Pomorski et al. have shown that gamma probe guided surgery after preoperative dose of 131I have allowed locating and increasing the completeness of thyroid excision. These results have been substantiated by other authors. However, in the evaluation of intraoperative gamma probe localization of 131I avid tissues one should remember of the limitations of the method. The article begins with a discussion of the statistical limitations of the radiation detection and of the key performance parameters that characterize detectors. Later on we continue with the description of specific aspects concerning gamma probe guided surgery in thyroid cancer.

[Early evaluation of treatment effectiveness using 131I iodine radiotherapy in patients with differentiated thyroid cancer]. / Ocena wczesnej skutecznosci leczenia uzupelniajacego jodem promieniotwórczym 131I chorych na zróznicowane raki tarczycy.

UNLABELLED: This paper presents the preliminary results of a prospective randomized trial on early effectiveness of 30 mCi versus 60 mCi for ablation of thyroid remnants in patients with WDTC after total thyroidectomy. Since April 1998 to January 2000, 220 patients with papillary thyroid cancer in stage T1b-3, N0-x, M0 had entered the study. 106 patients received 60 mCi and 114 received 30 mCi as the first ablation dose. The subject for the analysis was the uptake over the neck, post-therapeutic whole body scintigraphy and Tg level 6 months after ablation. The early effectiveness of ablation was estimated using a 5-degree scale: 0--very good effect, 1--good effect, 2--dubious effect-required repetition of WBS and Tg assessment in 6-12 months, 3--insufficient ablation--required repetition of radioiodine treatment, 4--for evident dissemination or local recurrence. RESULTS: Grades 0 were obtained in 29 (53%) after 30 mCi (group I) and in 38 patients (86%) after 60 mCi (group II). Grades 1 were obtained in group I in 15 patients (28%) and in 4 patients (9%) of group II. Grades 2 were obtained in group I in 9 patients (17%) and in group II in 1 (2.3%). Grade 3 was obtained only in 1 (2%) patient after 30 mCi. Grade 4 was obtained in one patient after 60 mCi (2.3%). The difference in uptake over the neck in the two groups was statistically significant (p < 0.05), although the differences in early effectiveness between the both groups according to the 5-degree scale were on the borderline of significance (p = 0.075). There was a correlation between uptake before and after ablation in 30 mCi group, which was not seen present in 60 mCi group. CONCLUSION: For the ablation of thyroid remnants 60 mCi should be considered as a standard dose.

[Use of recombinant human TSH for stimulation of iodine radioisotope uptake in metastases of thyroid cancer during therapy with 131I]. / Zastosowanie rekombinowanego ludzkiego TSH do stymulacji jodochwytnosci przerzutów raka tarczycy w czasie terapii jodem promieniotwórczym 131I.

The diagnostics with the use of recombinant human TSH for the follow-up of differentiated thyroid carcinoma (DTC) has been already approved. In more than 400 diagnostic scans, rhTSH proved to be effective in promoting 131I uptake in thyroid remnants and DTC metastases in patients receiving suppressive doses of thyroxine. However, information about its application in radioiodine treatment of DTC are scarce, especially with respect to patients with metastatic disease. In this review we have described our own results obtained during rhTSH aided radioiodine treatment of 42 patients with advanced DTC with reference to current literature data about diagnostic and therapeutic application of rhTSH.

[Use of 13-cis retinoic acid for treatment of advanced differentiated thyroid cancer]. / Zastosowanie kwasu 13-cis-retinowego w leczeniu zaawansowanego zróznicowanego raka tarczycy.

UNLABELLED: Retinoids, a large group of compounds structurally related to vitamin A, are able to induce redifferentiation of thyroid cancer cells. The aim of the study is to present our early results of retinoids redifferentiation therapy of thyroid cancer patients. In 15 patients with advanced thyroid cancer, whose cancer foci did not concentrate radioiodine, 13-cis retinoic acid (Roaccutan) was given for 6 weeks before radioiodine treatment. Radioiodine therapy was performed under exogenous TSH stimulation (Thyrogen). Three patients were treated twice. The planned retinoid dose was delivered to 11 patients. In the other four patients the reduction of retinoids dose was necessary due to severe side effects. In post-therapeutic scintigraphy radioiodine uptake was visible in two out of seven patients (29%) with lung metastases, in 5 out of 9 (56%) with locoregional disease and in two with bone metastases. On the whole, in 50% of patients reinduction of radioiodine uptake was visible, however, in most patients only a very discrete one. Thyroglobulin concentration before and after retinoids therapy did not differ significantly. CONCLUSIONS: In a subgroup of patients 13-cis retinoic acid can induce radioiodine uptake, however, prospective studies in larger groups of patients are necessary to prove its clinical application.

[Consequences of clinical genetic analysis of RET proto-oncogene]. / Konsekwencje kliniczne analizy genetycznej protoonkogenu RET.

Preliminary results of treatment of inherited medullary thyroid carcinoma, diagnosed primarily with genetic analysis of mutation of protooncogene RET are presented. Among 16 carriers of mutation identical with mutation diagnosed earlier in proband, there were 4 patients with clinically obvious medullary thyroid carcinoma and 12 asymptomatic carriers. In all patients, in whom calcitonin level was increased preoperatively, its normalization was obtained. The paper summarizes these aspects of cooperation between geneticians and physicians in which diagnostic results influence clinical decisions (indication and time of thyroid and lymph nodes surgery and it's spectrum, range of diagnostic procedures towards pheochromocytoma and parathyroid hyperplasia in relation to the found mutation).

[Proto-oncogene RET somatic mutations in medullary thyroid carcinoma]. / Mutacje somatyczne protoonkogenu RET w raku rdzeniastym tarczycy.

UNLABELLED: Somatic mutations of the RET protooncogene are present in 23-68% cases of sporadic medullary thyroid carcinoma (MTC). The aim of the study was to introduce the RET somatic mutations analysis in tumor tissue as well as to evaluate their types and frequencies in postoperative specimens of MTC patients treated in the Center of Oncology in Gliwice. MATERIAL: 14 tumor tissues obtained from sporadic MTC patients and two control groups--six and four specimens from patients with MEN 2A and MEN 2B syndrome respectively. METHODS: Tumor tissue DNA isolation followed by PCR amplification of RET exons 10, 11, 13, 14, 16 and automated, fluorescent sequencing of PCR products. We identified somatic mutation ATG > ACG in codon 918, exon 16 in 7 of 14 (50%) of analyzed sporadic MTC cases. We also found one deletion/insertion mutation in RET exon 11 that encompasses cysteine codon 634 and has not been published so far. The types and frequencies of found RET gene mutations were similar to previously reported. The analysis of RET somatic mutations supports the differentiation between the sporadic and inherited MTC. The presence of somatic mutation and its simultaneous absence in the germline proves sporadic type of cancer.

[Results of treating medullary thyroid carcinoma: the differences between sporadic and inherited forms]. / Wyniki leczenia raka rdzeniastego tarczycy: róznice pomiedzy postaciami sporadyczna i dziedziczna.

Medullary thyroid carcinoma (MTC) can be divided into two subgroups: sporadic or inherited. Hereditary form of MTC is often believed to be form with better prognosis than sporadic one. In this study the differences in MTC prognosis in Polish population of patients was analyzed. The group of 169 patients with MTC was examined. Hereditary cancer was stated in 48 (28%) patients. The median age of disease onset was 41 years (from 7 to 71 years). Genetic examination of RET protooncogene was performed in all patients. The calcitonin and CEA serum level analysis and radiological and radioisotopic examinations were used for monitoring of the disease course. Nineteen cases of MEN 2A syndrome, 11 cases of MEN 2B one and 18 cases of non classified familial MTC were recognized among patients with inherited MTC. Significantly lower age of disease onset in inherited MTC than in sporadic one was observed (27 years vs. 43.7 years, p < 0.001). Local or nodal recurrence was observed in 22 (13%) patients, distant metastases were stated in 21 (12%) patients. Basal or stimulated serum calcitonin level was increased in 85 (50%) patients. No significant differences between sporadic and inherited disease were observed. Eight patients died during observation, including 3 patients with sporadic MTC and 5 patients with inherited MTC. The updated 10-year survival rate was 97% in patients with sporadic MTC; in hereditary MTC it was about 20% worse. The complications related to the presence of adrenal tumors were the main reason for death in MEN2 and no significant differences in the course of MTC itself were observed.

The genetic background of medullary thyroid carcinoma in young patients.

The study was undertaken to evaluate the frequency of RET polymorphisms at codons 769 and 836 in young medullary thyroid carcinoma (MTC) patients in whom the presence of a known germline mutation has been excluded. 40 patients aged 10-29 were subjected to genetic analysis of RET exons 10, 11, 13, 14 and 16 and compared to 140 older patients. The hereditary component occurred to be very high in young MTC patients: 57% carry the germline mutation, other 28% exhibit at least one rare polymorphic variant of RET. The observed allelic frequencies were 38% for polymorphic variant L769CTG and 6% for variant S836AGT. The results were significantly higher than those obtained in the group of older patients: 20% and 1% for L769CTG and S836AGT, respectively. Our results speak in favour that the polymorphism in RET codon 769 and 836 may also be a factor predisposing to the development of MTC in young age.

Recombinant human TSH for the treatment of differentiated thyroid cancer metastatic to the spine.

The diagnostic use of recombinant human TSH (rhTSH) in follow- up of differentiated thyroid cancer (DTC) is already approved, however its application in (131)I therapy is still to be evaluated. We report results obtained in four patients with DTC metastatic to central skeleton, in whom 5 courses of rtTSH aided 131I therapy were administered.