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Cytokeratin 19 (CK19) is one of the most frequently studied immunohistochemical markers in thyroid pathology. The results of several studies suggest that CK19 may be useful in the diagnosis of papillary carcinoma, where it has been shown to have strong diffuse cytoplasmic reactivity. However, the published results vary, and the utility of CK19 in the diagnosis of thyroid lesions is controversial. The aim of this study was to evaluate, by Western blot analysis and the enzyme-linked immunosorbent assay (ELISA), the expression of CK19 in the cytosolic fraction obtained from 125 specimens of various thyroid lesions: nodular goiters, follicular adenomas, papillary carcinomas, follicular carcinomas and anaplastic carcinomas. The analysis of CK19 expression using the ELISA showed that the majority of papillary carcinoma cases had a much higher level of CK19 than did nodular goiters and adenomas (P

Calcitonin, the best known marker for medullary thyroid cancer (MTC), has several laboratory limitations which limit its use in the routines of non-specialized laboratories. Procalcitonin, the precursor of calcitonin, is free from these drawbacks. The aim of this study was to compare calcitonin and procalcitonin levels in MTC patients with active disease or in remission, and in patients with non-toxic nodular goiter (NTNG).Forty-three serum samples, obtained from 40 patients (6 MTC active disease patients, 23 MTC patients in remission, and 11 NTNG patients), were tested for calcitonin and procalcitonin levels. The levels of both markers were measured in 2 MTC patients with active disease before and after surgery. One was re-operated due to neck relapse, the other one due to liver metastases.Both procalcitonin and calcitonin levels were considerably higher in all MTC patients with the active disease. In two re-operated patients, the levels of both markers decreased after surgery but remained above the reference range. In the remission group of MTC patients, 18 had both markers within the reference range, 2 had slightly elevated calcitonin, and 3 patients exhibited both markers slightly increased. In the NTNG group, all but one patient had normal procalcitonin and calcitonin levels. Analysis revealed a significant correlation between procalcitonin and calcitonin levels (r = 0.7383; p0.0001).Procalcitonin has a similar distribution of values as calcitonin and may be used for evaluation of MTC status in some situations when accurate CT estimation is not achievable.

Background At present, researchers' attention has been concentrating on NDRG2 (N-Myc downstream-regulated gene 2) as a new gene candidate in the development and progression of papillary thyroid carcinoma (PTC). NDRG2, together with NDRG1, NDRG3 and NDRG4 are members of the NDRG family, a new class of genes, inhibited by N-Myc oncogene. Aim The aim of our study was to evaluate NDRG2 mRNA expression in the primary PTC and its metastases to regional lymph nodes. Materials and methods Postoperative tissue and macroscopically changed lymph nodes of sixteen (16) patients with PTC constituted the studied material. In this group, metastases of the cancer to regional lymph nodes were confirmed histopathologically in 8 cases. Quantitative evaluation of NDRG2 mRNA expression was performed by the real-time polymerase chain reaction (real-time PCR) method. Results The mean values of NDRG2 mRNA expression in the primary tumour tissues were statistically significantly lower vs. the levels of NDRG2 mRNA expression in macroscopically unchanged thyroid tissue (p < 0.0001). A comparison of the mean NDRG2 mRNA expression of primary tumours and that of their metastases to regional lymph nodes did not demonstrate any statistical differences (p > 0.05). A positive correlation was observed between NDRG2 mRNA expression in primary tumour cells and in the cancer metastases to lymph nodes (Rs = 0.7857; p < 0.05). Factors, such as age, sex, tumour stage in TNM system, were of no significance for NDRG2 mRNA expression level (p > 0.1). Conclusion The results of our study demonstrated decreased NDRG2 mRNA expression levels in PTC, when compared to macroscopically unchanged thyroid tissue, which may point to the potential role of NDRG2 in the development and progression of cancer in question.

Single N-acetylglucosamine residues attached by O-linkage to serine or threonine (O-GlcNAc) are an abundant, dynamic and inducible post-translational modification of cytoplasmic and nuclear proteins. This study analyzes the activity of the enzyme involved in the removal of these sugar residues, i.e. beta-N-acetylglucosaminidase (O-GlcNAcase) as well as the level of O-GlcNAc in benign and malignant thyroid lesions. Our results demonstrate increased activity of the enzyme in thyroid cancers in comparison to non-neoplastic lesions and adenomas. O-GlcNAc-modified proteins in thyroid cells have a predominantly nuclear distribution and are more abundant in non-neoplastic lesions than in tumors. Understanding the aberrant O-GlcNAc metabolism in thyroid cancer cells may be helpful for developing new diagnostic or treatment methods.

Aims and backgroundThe increased expression of galectin-1 on the mRNA and protein level observed in malignant thyroid tumors in comparison with benign lesions suggests that this protein may be associated with malignant transformation of thyroid epithelium. Extracellular and membrane glycoproteins are the main known ligands for this galactose-binding lectin. However, immunofluorescence studies have shown that galectin-1 is found predominantly in the intracellular compartment. The aim of this study was to examine intracellular carbohydrate ligands of galectin-1 in the thyroid, with particular attention to potential differences in their expression levels between benign and malignant lesions.MethodsIdentification of cytosolic and nuclear glycoproteins binding galectin-1 was performed by affinoblotting after separation of proteins in 8% polyacrylamide slab gels and electrotransfer onto Immobilon-P membranes. For semiquantitative analysis of glycoproteins binding galectin-1, an enzyme-linked lectino-solid-phase assay (ELLSA) was used.ResultsThe predominant cytosolic glycoproteins binding galectin-1 had molecular masses of 50, 55, 59, 64, 85–87, 100, and 133 kDa and nuclear glycoprotein had a molecular mass of 75 kDa. There were no evident differences in glycoprotein patterns between benign and malignant thyroid lesions. The results obtained by ELLSA did not show any significant differences in lectin binding by cytosolic and nuclear proteins of thyroid lesions either.ConclusionsOn the basis of these results it is tempting to suggest that interactions between galectin-1 and intracellular glycoconjugates are not critical for malignant transformation in the thyroid gland.

Papillary thyroid microcarcinoma is a particular form of cancer of the thyroid gland. This term, according to the WHO classification, is applied to papillary tumors no larger than 1.0 cm in diameter, which are incidentally detected during the postoperative histopathological examination. In clinical practice, the term pertains to all papillary tumors of the size smaller than or equal to 1 cm. The aim of the study was to determine the prevalence of papillary thyroid microcarcinoma and its selected histopathological characteristics among patients with malignant cancer of the thyroid gland identified in our own material in the years 2000-2007. Material and methods. The study included 523 patients treated for thyroid carcinoma: 401 (76.7%) women and 122 (23.3%) men aged 12-83 years (mean 49.8 years). Surgeries were carried out according to the Polish Group for Endocrine Carcinomas recommendations, in compliance with the European consensus. Results. Papillary thyroid carcinoma was identified in the postoperative histopathological examination in 391 (74.8%) patients; 285 (72.9%) women and 106 (27.1%) men. Their age ranged from 14 to 75 years (mean 49.3 years). Among 391 cases, tumor progression classified according to the WHO criteria (3) was as follows: T1 in 260 (66.5%), T2 in 59 (15.1%), T3 in 53 (13.5%) and T4 in 19 (4.8%) patients. In 150 cases (38.4% of papillary tumors), the tumor fulfilled the morphological criteria for microcarcinoma (4) and was detected in 118 (78.7%) women and 32 (21.3%) men. Carcinoma was identified in the neutral goiter in 138 cases, and in 12 patients in hyperactive, including 9 in nodular and 3 in Graves’ goiters. The disease was suspected or diagnosed preoperatively or at surgery in 112 patients. Postoperative diagnosis was performed in 38 (25.3%) individuals with micrcarcinoma. Twenty-four (38%) of 63 patients with multifocal tumors were subjected to adjunctive surgery as their cancer diagnosis was made only postoperatively in the histopathological examination. The subcapsular location of microcarcinoma was found in 78 (49.4%) cases including capsular infiltration and extracapsular invasion in 14 patients. The exact histopathological examination showed multifocality in 63 (42%) cases and involvement of the local lymph nodes in 29 (19.3%) patients. In 21 cases, the central compartment lymph nodes were involved. The presence of metastases in the central and lateral lymph node compartment was observed in 5 cases; in 3 patients skip metastases were detected in the lateral compartment on the tumor side omitting the central compartment. No patient with microcarcinoma diagnosed between the years 2000 and 2007 revealed distant metastases. Conclusions. Due to contemporary diagnostics, papillary thyroid microcarcinomas – tumors up to 1 cm – are most commonly identified cancers of the thyroid gland. High accuracy of US-guided fineneedle aspiration biopsy of high resolution permits to diagnose the majority of these tumors prior to surgery.

The aim of the prospective study was the evaluation of primary, subclinical, normocalcemic hyperparathyroidism (PHPT) incidence in patients, operated on because of non-toxic (NTG), toxic (TG) goiter and papillary thyroid cancer (PTC).The study was performed in the group of 196 patients operated on NTG (115 patients), TG (43 patients) and PTC (38 patients). All patients had never been operated because of goiter. No patient had clinical symptoms of PHPT. Calcium concentration (Ca), phosphorus concentration (P) and alkaline phosphatase activity (ALP) in blood serum were measured in all patients a day before operation. When those parameters were out of range, parathormone concentration (PTH) in blood serum was measured. In the case of elevated PTH concentration PHPT was diagnosed. Furthermore, in order to exclude renal failure and insufficiency tests for creatinine and urea concentrations in blood serum and urinalysis were performed.There was no case of increased Ca concentration among 158 patients with benign goiter. The values of at least one measured parameters (P or ALP) were abnormal in 47 out of 158 patients with benign goiter (29.7%). Increased PTH concentration (mean 101.5 pg/ml) was in 16 of 47 patients (10.1% of 158 patients). Normocalcemic PHPT was diagnosed in 12 (10.4%) NTG patients and 4 (9.3%) TG patients. In patients with PTC hypercalcemia was not affirmed. In 7 (18.42%) cases of 38 PTC patients P concentration and ALP activity were abnormal. Increased PTH concentration (84.85 pg/ml) was found in one female with PTC with normal values of P and ALP. Incidence of PHPT was observed in 2.63% of PTC patients.1. There was no significant difference of PHPT incidence between various type of goiter. 2. In our study coexistence of PTC and normocalcemic, asymptomatic PHPT is rare.

We sought to assess whether extensive surgical treatment, postsurgical radioiodine therapy, or both decrease the risk of locoregional recurrence (LR) after curative primary treatment in children and adolescents diagnosed with differentiated thyroid cancer (DTC) at ageor=18 y.To determine the incidence of and identify predictive factors for thyroid bed recurrence (TBR) or lymph node recurrence (NR), we performed a chart review and retrospective multivariate Cox regression analysis on 235 patients with DTC diagnosed at ageor=18 y and managed with curative intent at our tertiary referral center from 1973 to 2002; 40 of these patients had distant metastases at diagnosis. We also determined overall and recurrence-free survival and generated curves for these variables using Kaplan-Meier and Cox univariate analysis.During a median follow-up of 82 mo (range, 5-402 mo), no DTC-related deaths occurred, 203 (86%) children remained recurrence-free, and 32 (14%) children had LR, including TBR in 9 (28% of LR), NR in 20 (63% of LR), and both in 3 (9% of LR). Among patients treated with radical intent and showing no distant metastases, the most recent thyroglobulin level was1 ng/mL in all but 4% of cases. The median time from the first surgery to LR was 37 mo (range, 9-280 mo). In multivariate analysis, significant risk factors for TBR were less than total thyroidectomy and lack of postsurgical radioiodine treatment (respective risk increases of 9.5 [P = 0.04] and 11 times [P = 0.03]). For NR, classic papillary histology, incomplete primary lymph node management (i.e., lack of modified lymphadenectomy of affected lymph nodes or lack of confirmation of disease-free nodes by intraoperative staging), and absence of adjuvant radioiodine therapy were independent significant predictive factors that increased the recurrence risk by 1.9 (P = 0.02), 3.3 (P = 0.02), and 3.2 (P = 0.02) times, respectively. Age or sex did not correlate with LR risk.In DTC patientsor=18 y of age, extensive initial therapy-consisting of total thyroidectomy combined with modified lymphadenectomy performed in case of lymph node metastases and followed by radioiodine therapy--is associated with a substantial decrease of DTC LR risk.

Enhanced sialylation represents one of the most frequently occurring alterations of the sugar chain structure in various cancers. However, up to now, sialylation of intracellular proteins of thyroid carcinomas has never been investigated. The aim of this study was comparative analysis of cytoplasmic and nuclear sialoglycoproteins isolated from thyroid benign and malignant tumors as well as non-neoplastic lesions. The sialylation level and types of sialic acid linkages were analysed by lectin blotting and enzyme linked lectino-solid-phase assay (ELLSA) using Sambucus nigra (SNA) and Maakia amurensis (MAA) agglutinins. The presence of alpha2,6 and alpha2,3 linked sialic acid residues was detected in all types of thyroid lesion specimens but there were some differences in the banding and intensity patterns. Analysis of SNA and MAA binding by ELLSA method showed that in the majority of cancer samples the level of sialic acid residues was lower than in non-neoplastic lesions and adenomas. Our present results suggest that decrease in sialylation rather than increase is a characteristic feature of malignant transformation in the thyroid.

Medullary thyroid carcinoma (MTC) is usually more advanced at presentation than differentiated thyroid cancers and often has distant metastases. The primary treatment of MTC is total thyroidectomy and regional lymph node dissection. The efficacy of these procedures has been limited by the aggressiveness of the disease and metastatic spread at the time of surgery. Persistently elevated levels of calcitonin (CT) and carcinoembryonic antigen (CEA) or their increase postoperatively are indicative for residual or recurrent disease. Conventional imaging methods such as ultrasonography, computed tomography, magnetic resonance imaging and MIBI scintigraphy usually fail to find the source of calcitonin. Better imaging properties have been shown by DMSA scintigraphy, somatostatin receptor scintigraphy or by positron emission tomography (PET). The aim of the study was to evaluate the diagnostic accuracy of PET for the localisation of occult MTC in patients after surgery with increased concentrations of CT, in whom conventional imaging procedures have not been successful.The PET investigation using (18)F-fluoro- 2-deoxy-D-glucose combined with computed tomography ((18)FDG-PET/CT) was performed at the Department of Nuclear Medicine (Oncology Centre in Bydgoszcz) between January and October 2004. In five patients with postoperative calcitonin ranging from 164 to2000 ng/l (normal10 ng/l) no tumour lesions were found using other imaging methods.In four of five cases, responsible lesions with a higher metabolism of FDG, indicating MTC tissue (remnants or metastases), were localised. In one patient no focus of FDG accumulation was found despite high CT concentration. PET detected tumour manifestations in the neck and the mediastinum in two patients, in the lung and the left adrenal gland in one case and in the neck and the liver in another patient. As a result of surgery for the removal of a residual tumour or metastases the accuracy of diagnosis was confirmed by histopathology in all four cases and a decrease in CT and CEA levels was observed in 3/4 cases. The metabolic imaging findings by PET/CT ensured that the surgery on these patients was successful.For the detection of occult residual or metastatic MTC lesions, (18)FDG-PET is a valuable procedure in imaging diagnostics.

The optimal surgical treatment of children with differentiated thyroid cancer remains an important point of discussion. Especially the need for completion operation is questioned in young patients. Our objective was to examine the rate of residual neoplastic disease after non radical initial operation.From the 235 children diagnosed with differentiated thyroid cancer, 131 (56%) needed completion operation due to incomplete primary surgery. Completion operation involved thyroid bed, lymph nodes or both respectively in 91 (39%), 13 (6%) and 27 (11%) cases. Risk factors responsible for residual disease were evaluated by means of logistic regression analysis.Residual disease was detected in 46 (35%) of reoperated children (25% in thyroid bed and 85% in lymph node of lateral neck compartment). Sex and age did not influence the risk of residual disease in thyroid bed or lymph nodes. Papillary type of cancer and multifocality increased risk of residual disease in thyroid bed respectively by the factor of 15 (95% CI: 2-125) and 2.3 (95% CI: 1.2-4.4). Infiltration of thyroid capsule did not correlate with the risk of residual disease. Lymph node metastases in primary operation increased risk of residual disease by the factor of 16 (95% CI: 1.2-245). Histopathology, multifocality of primary tumour or infiltration of lymph node capsule did not influence the risk of residual disease in lymph nodes of lateral neck compartment.In children with differentiated thyroid cancer residual disease is diagnosed in about 1/3 of non radically operated cases. This high incidence justifies completion operations. The risk of residual disease is significantly increased in papillary thyroid cancer, multifocal tumours and cases with lymph node metastases.

Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes.The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology.Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology.1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

Total thyroidectomy with lymphadenectomy is the most typical operation in a case of papillary thyroid cancer. Range of lymph node resection still remains a matter of controversy. In some publications treatment of lymph node metastases doesn't affect survival, so only selective lymph node resection is the extended enough operation. The others remark that, local relapse- the worst prognostic factor, appears the most often in the lymph nodes, so they suggest more aggressive treatment. To solve that problem we try to find more sensitive methods to examine lymph nodes.To compare the results of detection lymph node metastases of papillary thyroid cancer by immunohistochemistry with the results of RT- PCR for thyroglobulin (Tg) mRNA.Each of one hundred eighty four cervical lymph nodes obtained from 24 patients, operated in our Department was divided into 2 halves: one was used for conventional histopathology and immunohistochemistry, the other part was investigated by RT- PCR for Tg mRNA. Immunohistochemical staining for Tg was performed on formalin-fixed, paraffin-embedded sections with anti-Tg antibodies.According to routine, histopathological examination 8 (33.5%) patients had involved lymph nodes. One hundred correspondence of the results of immunohistochemistry and histopathology was observed. We obtained different results of examination of the lymph nodes in 6 (25%) patients. In four patients (16.7%) RT-PCR was more sensitive in detection of positive lymph nodes, in two patients (8.3%) it revealed less metastasized lymph nodes than immunohistochemistry. The remaining 18 patients didn't have any differences, fourteen (58.3%) of them had the negative lymph nodes and four (16.7%) had positive, the same lymph nodes in all examinations. Finally, according to RT-PCR 10 (41.7%) of the patients had metastasized lymph nodes.Tg RT-PCR is a sensitive method of detection of papillary thyroid cancer cells and may help to detect the metastases of papillary thyroid cancer in regional lymph nodes.

NIS gene is located on chromosome 19 and encodes 643 amino acid protein. It belongs to membrane Na+ dependent glucose symporter proteins family. In normal thyroid is located in basolateral membrane of thyreocyte. It plays a main role in concentrating of iodine in thyreocyte and thus in thyroid hormones synthesis. It was proved that NIS expression influences effectiveness of radioactive iodine therapy in well-differentiated thyroid cancers. The aim of this study was to estimate the NIS expression and its dependence with gender, age and stage in thyroid papillary and follicular cancers. The frozen sections of tissue were used as a source of tumor RNA. RT-PCR technique was employed for NIS expression analysis. We did not find dependence between the presence of NIS expression in investigated thyroid cancers and stage of disease estimated according to TNM classification. We also did not find dependence between NIS expression and gender or sex of the patients. Our results suggest that there is no dependence between NIS expression and iodine uptake.

Neoplastic angiogenesis is an essential stage of growth, progression and invasion of solid tumours. The process of basement membrane degradation and remodelling of the extracellular matrix (EMC) involves proteolytic enzymes called metalloproteinases. Among the numerous proteolytic enzymes of this group the key role is played by metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2). Tissue expression and concentration of these compounds in body fluids have been used in early diagnostics of tumours development, assessment of tumours advancement and treatment results monitoring. The aim of the study was to evaluate the concentration of MMP-2 and TIMP-2 in blood serum of patients with benign and malignant thyroid tumours and the effect of surgical treatment on these parameters in the postoperative period as well as assessment whether to MMP-2 and TIMP-2 serum concentration in patients with thyroid cancer positively correlates with the clinical staging classification of the International Union Against Cancer (UICC).The study group consisted of 53 patients with various types of thyroid cancer and 23 patients with benign thyroid tumours, while 26 healthy adults served as controls. According to clinical staging classification of thyroid cancer the 32 patients were classified with stage I, 6 with stage II, 8 with stage III and 7 with stage IV. We have found higher mean concentration of MMP-2 in 53 patients with thyroid cancer as compared to the control group and the group of 23 patients with benign thyroid tumours. All patients were treated operatively. Additionally, a significant effect of radical surgical treatment on mean concentration of MMP-2 and TIMP-2 in patients with papillary and follicular thyroid cancer was demonstrated.MMP-2 and its tissue inhibitor TIMP-2 apparently play a significant role in the pathogenesis of thyroid cancer. Evaluation of their concentration in peripheral blood serum may be useful for the differentiation between benign and malignant thyroid tumours. Serum MMP-2 and TIMP-2 concentrations in patients with thyroid cancer did not significantly correlate with the clinical staging of thyroid cancer.

The range of lymphadenectomy in differentiated thyroid cancer remains still a matter of controversy because of the lack of reliable diagnostic methods for nodal metastases, other than histopathology. To compare the results of detection of lymph node metastases of papillary thyroid cancer by conventional histopathology and immunohistochemistry with the results of reverse transcription–polymerase chain reaction for thyroglobulin mRNA. Each of 166 cervical lymph nodes obtained from 21 patients was divided into two halves: one was used for conventional histopathology and immunohistochemistry, the other part was investigated by molecular examination. We obtained different results from examination of the lymph nodes in six (28.6%) patients. In four patients (19.1%) reverse transcription–polymerase chain reaction (RT-PCR) was more sensitive in detection of positive lymph nodes; in two patients (9.5%) it revealed fewer metastasised lymph nodes than did histopathology. The rest of the patients did not have any differences: 12 (57.1%) of them had negative lymph nodes and three (14.3%) had positive lymph nodes in all examinations. (1) Thyroglobulin (Tg) RT-PCR is an appropriate method of detection for thyroid cancer cells. (2) In combination with histopathology, it might help to qualify patients’ nodal status better.

Differences in glycosylation of nuclear and cytosolic proteins isolated from benign and malignant human thyroid neoplasms were analyzed by lectin blotting and enzyme linked lectino-solid-phase assay using Erythrina cristagalli and Ricinus communis agglutinins. The results reported in this study have not shown any significant differences in lectin binding by nuclear proteins of benign and malignant tumors, however, quantitative and qualitative differences were observed in the patterns of cytosolic glycoproteins. In the majority of carcinomas samples lectin binding to cytosolic proteins was definitely weaker in comparison with adenomas and non-neoplastic specimens, which suggested alterations in glycosylation of cytosolic proteins in malignant tumors.

From 1974 to 1999, 1,001 patients were operated on for thyroid cancer, including 778 (78%) for differentiated thyroid cancer and 223 (22%) for other thyroid malignant neoplasms. Radical operations were performed in 716 (92%) patients with differentiated thyroid cancer and in 85 (38%) patients with other thyroid malignant neoplasms. After surgery, all patients underwent various methods of complementary treatment, depending on cancer type and grading (levothyroxine, 131I, radiotherapy and/or chemotherapy). These patients had no evidence of persistent disease after finishing treatment (Tg, CEA, calcitonin, scintigraphy). We observed recurrences of thyroid cancer, although macroscopic, microscopic, biochemical, and scintigraphic criteria of radicality were present. At 18 months' to 24 years' follow-up, we observed recurrences in 94 (11.7%) of 801 patients treated radically, including in 53 (7.4%) of 716 patients with differentiated thyroid cancer and in 41 (48%) of 85 patients with other thyroid malignancies. Among 37 patients with thyroid bed recurrence, 18 (48.6%) underwent radical operations and 19 (51.4%) palliative ones. Of 33 patients with regional lymph node recurrence, radical operations were performed in 26 (78.8%) and palliative ones in seven (21.2%). Of 24 patients with distant metastases, four (17%) (with single metastasis) underwent surgery (three radical operations and one palliative one). Other methods of treatment were used in the remaining patients. Occurrence of thyroid cancer recurrences in the thyroid bed and lymph nodes indicates that macroscopic, microscopic, and scintigraphic criteria of radicality are not sufficient. Recurrences after radical surgery are more infrequent in patients with differentiated thyroid cancers than in those with other thyroid malignant neoplasms. In many patients, thyroid bed and lymph node recurrences can be removed radically during surgery.

From the contents: The urokinase receptor (uPAR, CD87) as a target for tumor therapy Molecular regulation of urokinase receptor (u-PAR) gene expression as one potential concept for molecular staging and therapy Stromal cell involvement in cancer Inhibition of the tumor-associated urokinase-type plasminogen activation system: effects of high level synthesis of soluble urokinase receptor in ovarian and breast cancer cells in vitro and in vivo Molecular mechanisms of carcinogenesis in gastric cancer Clinical implications of molecular diagnosis in HNPCC Minimal residual disease in gastric cancer Minimal residual disease in breast cancer and gynecological malignancies Clinical implications of the EGF-receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options Minimal residual disease in the bone marrow and peripheral blood of patients with metastatic breast cancer Estrogen receptor (ER) expression profile of disseminated epithelial tumor cells in the bone marrow of breast cancer patients Detection of circulating tumor cells in blood using an optimized density gradient centrifugation Antitumoral and antimetastatic effects of continuous particle mediated cytokine gene therapy Genetic subtyping of renal cell carcinoma by comparative genomic hybridization Telomere length and hTERT expression in patients with colorectal carcinoma Evaluation of the level of bFGF, VEGF, sICAM-1, sVCAM-1 in the serum of patients with thyroid cancer.

This paper reports macro- and microscopic changes in hyperfunctioning thyroid nodules (HTN), initially diagnosed as solitary, in patients treated with percutaneous ethanol injection (PEI). In 78 patients, benign solitary HTN were diagnosed by clinical and hormonal examination. High resolution ultrasonography confirmed the solitary nodule. The results of fine needle aspiration biopsy (FNAB), performed twice, ruled out malignancy of the nodule. The patients were referred for PEI treatment. At 1-year follow-up, newly formed thyroid nodules, whose volumes increased, were detected in five patients (6.4%) with HTN, initially diagnosed as solitary. Therefore, these patients were operated on. Subtotal thyroidectomy was performed. At the intraoperative macroscopic evaluation, a hard fibrous solid mass was found in place of three nodules (n1, n2, n3) following PEI treatment. The middle area of the cut surface of PEI-treated nodules (n4 and n5) in the other two patients was firm and haemorrhagic, surrounded by a fibrous mass. Histolopathologic examination of n1, n2 and n3 revealed fibrosis and hyalinosis. Examination of n4 and n5 showed haemorrhagic necrosis in the middle of the nodules surrounded by fibrous tissue.

The aim of this study was to investigate post cryotherapy thyroid function status of normal rat thyroid tissue and to determine the topography of temperature of cryotreated tissues and of tissues adjacent to them. Nitrous oxide cryotherapy was performed in 40 male Wistar rats. They were divided into four groups of 10. In group I, the right thyroid lobe was subjected to cryotherapy and the left lobe was not frozen. In group II, both thyroid lobes were cryotreated. In group III, the right lobe was frozen and the left lobe was excised. In group IV, the thyroid was subjected to neither cryotherapy nor surgery. During cryotherapy, the temperature in various places of the thyroid and in the surrounding tissues was measured. Serum thyrotropin concentrations were determined before an experiment and 4 weeks after in all rats. The results of temperature measurements proved that it is possible to limit cryotherapy to certain areas of thyroid tissue and to spare the neighboring tissues, because they are not subjected to temperatures that are damaging. The effectiveness of cryotherapy was confirmed by functional effect. Cryotherapy changed function of thyroid tissue. There was a statistically significant difference between mean baseline and follow-up concentrations in rats of groups II and III. In both groups hypothyroidism occurred post cryotherapy.

In recent years cryotherapy has been more and more frequently used for the treatment of tumors of different organs. Until now, the use of cryotherapy for the treatment of thyroid lesions, as well as histopathologic changes in thyroid tissue after cryotherapy, has not been described. Nitrous oxide cryotherapy of one thyroid lobe in twenty 12-week male Wistar rats was performed. After 2 and 4 weeks, the cryotreated thyroid lobe and the second lobe along with a part of the trachea, esophagus, and the subhyoid muscles adhering to the thyroid were excised and assessed macro- and microscopically. The macroscopic evaluation, performed 2 and 4 weeks postcryotherapy, revealed atrophy of the cryotreated lobe in 4 and 3 rats, respectively, and reduction of the cryotreated lobe dimensions in 6 and 7 rats, respectively. In the specimens of the lobes excised 2 weeks following cryotherapy, examined microscopically, necrosis, granulomatous inflammation, hemorrhages, and hemosiderin deposits were found most often, whereas in the specimens of the lobe excised after 4 weeks lymphocytic inflammation and fibrosis were mainly observed. No microscopic changes were observed in the thyroid lobes that were not frozen or in the parathyroid glands located inside these lobes or extrathyroidally, either ipsilaterally or contralaterally to the cryotreated thyroid lobes. There was no microscopic damage to other tissues adjacent to the thyroid gland. No rat developed vocal cord dysfunction after cryotherapy and no significant changes in serum calcium level before and after cryotherapy were observed. The results obtained show that it is possible to cryoblate thyroid tissue without damaging the tissues adjacent to the thyroid, as well as to spare function of the recurrent laryngeal nerves and parathyroid glands.

The serine/threonine protein kinase Akt is a key molecule in the phosphatidyl inositol 3-kinase pathway that is often overactivated in human cancers. Three Akt isoforms (Akt1, Akt2, Akt3) have been identified in human cells and they show different distribution and have non-redundant functions. The aim of this study was to determine whether the expression, phosphorylation, and localization of Akt1 isoform in human thyroid malignant lesions are different from those in benign lesions. Nuclear and cytoplasmic fractions were isolated from tissue samples and Western blot method was used to detect Akt1 presence in both cellular fractions. Akt1 expression was also assessed by ELISA method. To estimate Akt1 phosphorylation, kinase was immunoprecipitated from cell lysates and tested with anti-phospho-Akt antibodies. The Akt1 expression in majority of thyroid cancer samples was significantly higher than in benign lesions (p

In the present study the role of tumour suppressor genes (TSGs) hypermethylation and genetic instability of LOH/MSI type in thyroid tumorigenesis was assessed. Expression, methylation status and presence of LOH/MSI were analyzed for 8 TSGs selected from imprinted (IR) and non-imprinted (NIR) chromosomal regions in papillary thyroid carcinomas (PTCs) and nodular goitres (NGs). The results show that methylation-induced gene silencing occurs at an early step of thyroid carcinogenesis and involves multiple genes. Genetic changes of LOH/MSI type are less frequent. In PTC samples, the lack of significant differences in the frequency of LOH in IR and NIR suggests that it is not a key mechanism changing the pattern of gene expression. Co-methylation observed both in NG and PTC raises a possibility that, in thyroid tissue, methylation-induced silencing may occur not only in malignant transformation but also in functional context. We did not recognize any of the studied TSGs - in regard to aberrant methylation status or LOH/MSI frequency - as a selective molecular marker in thyroid tumorigenesis.