Biomedical subjects

Jan Włoch

Publications and source records attributed to Jan Włoch.

At least 19 recordsLinked to original sources

PubMed2006

Molecular analysis of the RET and NTRK1 gene rearrangements in papillary thyroid carcinoma in the Polish population.

Among different genetic factors involved in the pathogenesis of the papillary thyroid carcinoma (PTC), rearrangements of RET protooncogene (RET/PTC), as well as rearrangements of NTRK1 protooncogene are best known. The resulting hybrid oncogenes are found in PTCs with variable frequency, depending on the examined population. The relationship between these chromosomal aberrations and clinical outcome of PTCs remains still controversial. The study aimed at estimating the frequency of rearrangements of RET and/or NTRK1 protooncogenes in PTC in the Polish population, and at evaluating the possible relationships between the presence of RET and/or NTRK1 oncogenes and such parameters, as patient's age, gender, histopathological variant of tumor and clinical staging. Expression analysis of RET and NTRK1 was performed by duplex reverse transcription-polymerase chain reaction (duplex RT-PCR) and OneStep RT-PCR, respectively, in tumor tissues obtained from 33 patients with PTC. Rearrangements of the RET protooncogene (RET/PTC1, RET/PTC2 and RET/PTC3) were detected in 7 out of 33 PTC (21%), and rearrangements of NTRK1 [Trk-T1 and Trk(TPM3)] were detected in 4 out of 33 examined samples (12%). In none of the examined cases, did the RET and NTRK1 rearrangements occur in the same sample. No correlations were found between RET/PTC or Trk oncogenic sequences and patient's age, gender, the histopathological variant of PTC and the assignment to particular stage in clinical staging systems (TNM Staging, the University of Chicago clinical class, and Ohio State University Staging). Our study is the first one in which the frequency of NTRK1 rearrangements in PTC was reported for the Polish population. On the other hand, the frequency of RET rearrangements in PTC, as found by us, was similar to the previously reported results for the Polish population. Our results do not confirm the relationship between the structural aberrations in question and the clinical outcome of PTC.

Adolescent↗

PubMed2006

[Expression of DPP4 gene in papillary thyroid carcinoma].

INTRODUCTION: DPP4 gene (dipeptidyl peptidase IV) is expressed in epithelial cells of many organs and cells of immune system. There is no expression of DPP4 in normal healthy thyroid, while it is highly expressed in papillary thyroid carcinoma (PTC), as shown by gene expression profiling. In this study we validated expression of DPP4 in papillary thyroid cancer and normal thyroid tissue and evaluated its usefulness for diagnostic purposes. MATERIAL AND METHODS: The analysis was carried out on total RNA extracted from 102 PTCs and 77 normal thyroid fragments with use of Q-PCR reaction. Beta-glucuronidase was the reference gene. RESULTS: We confirmed the distinct increase of DPP4 expression in papillary thyroid carcinoma. However, the ROC (relative operating characteristic) analysis revealed that the diagnostic efficiency of DPP4 estimation is limited. CONCLUSIONS: DPP4 is increased in papillary thyroid cancer, however, its diagnostic usefulness as a single PTC marker is doubtful.

Adolescent↗

PubMed2005

Analysis of cyclin D1 and retinoblastoma protein immunoreactivity in follicular thyroid tumors.

Protein products of cyclin D1 and retinoblastoma (Rb) genes play crucial roles in regulation of G1/S transition in the cell cycle. In this study we analyzed, using immunohistochemical methods, the expression of cyclin D1 and Rb proteins in material from medical archives (12 cases of follicular thyroid carcinoma, 57 cases of follicular adenoma and 17 nodular goiter cases). A positive nuclear reaction for cyclin D1 was observed in 83.3% (10/12) of the follicular carcinomas, in 96.5% (55/57) of the follicular adenomas and in 23.5% (4/17) of nodular goiters. Overexpression of cyclin Dl (more than 50% of positively staining cells) was noted in 25% (3/12) of the follicular carcinomas and in 22.8% (13/57) of the follicular adenomas. No overexpression of cyclin D1 was noted among nodular goiters. The number of carcinoma cases with cyclin D1 overexpression did not differ statistically in any significant way from the follicular adenoma group (p = 1.000). A positive nuclear reaction for Rb protein was noted in 100% of the follicular carcinomas (12/12), in 96.5% of the follicular adenomas (55/57) and in 47.1% of the cases (8/17) of nodular goiter. Rb protein overexpression (more than 50% of positively staining cells) was found in 83.3% (10/12) of the follicular carcinomas, in 68.4% (39/57) of the follicular adenomas and in 11.8% (2/17) of the nodular goiters. The number of cases with Rb protein overexpression in the follicular carcinoma group did not differ significantly from that in the follicular adenoma group (p = 0.486). A positive correlation was found in the groups studied between the expressions of Rb protein and cyclin D1. However, the correlation was statistically significant only in the nodular goiter group (Rs = 0.567; p = 0.018). In the follicular carcinoma group, that correlation was borderline (Rp = 0.437; p = 0.072) and, in the follicular adenoma group, it was statistically insignificant (Rs = 0.217; p = 0.105). Our results confirm the existence of mutual regulation mechanisms of Rb and cyclin D1 protein expressions, which are observed in cells from various carcinomas.

Adenocarcinoma, Follicular↗

PubMed2004

RET polymorphisms in codons 769 and 836 are not associated with predisposition to medullary thyroid carcinoma.

The study was undertaken to verify whether the RET gene polymorphisms are associated with MTC in patients negative for germline mutations. Two hundred five patients with apparent sporadic MTC were subjected to genetic analysis of RET exons 10, 11, 13, 14, 16 and 22 RET germline mutation carriers were identified with 10.7% frequency. The frequency among 26 patients not older than 30 was 27%. In patients excluded for known mutations we analyzed two polymorphic sites: RET codon 769 and 836. As control group, 90 healthy subjects were investigated. In young patients the observed allelic frequencies were 32% for variant L769/CTG and 5% for variant S836/AGT. Although these values were higher than in older MTC patients (22 and 3%, respectively), as well as in the control group (27 and 2%) the difference was insignificant. We conclude that in Polish patients polymorphisms at RET codons 769 and 836 are not associated with medullary thyroid carcinoma.

Adolescent↗

PubMed2004

Expression of insulin-like growth factor I (IGF-I) gene and of genes for IGF-binding proteins 1, 2, 3, 4 (IGFBP-1-IGFBP-4) in non-neoplastic human thyroid cells and in certain human thyroid cancers. Effect of exogenous IGF-I on this expression.

AIM: The aim of this study was to examine the expression of the IGF-I gene and of genes for IGFBP-1, -2, -3, and -4 in cells from nodular goiters (NG), and from different human thyroid carcinomas (papillary--PTC, anaplastic--ATC, and medullary--MTC), cultured in monolayers. The influence, exerted by exogenous IGF-I on the expression of these genes, was also investigated. METHODS: Thyroid tissue specimens were obtained from 65 patients during subtotal or total thyroidectomies. After approximately 2-3 weeks of culture, thyroid cells were incubated for 24 hours with IGF-I in concentrations of: 0, 1, 10 and 100 ng/ml. The total mRNA was isolated according to the method described by Chomczyński and Sacchi with our own modifications. Afterwards, mRNA encoding IGF-I, IGFBP-1-IGFBP-4 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were amplified, using the reverse transcription-polymerase chain reaction (RT-PCR); GAPDH gene served as a control gene. PCR products were electrophoresed and then submitted to densitometric analysis. RESULTS AND CONCLUSIONS: Our study has shown that in carcinoma cells (ATC, PTC, MTC), IGF-I reveals a stimulatory influence on the expression of its own gene, that effect being most distinctive in ATC cells. These facts indicate an important role of IGF-I in the pathogenesis and invasiveness of the analyzed malignant neoplasms.

Adolescent↗

PubMed2004

Analysis of P53 and P21WAF1 proteins expression in follicular thyroid tumors.

The expression of P53 and P21WAF1 proteins was analyzed immunohistochemically in archival material derived from 12 cases of follicular thyroid carcinoma, 57 cases of follicular adenoma and 17 cases of nodular goiter. In the follicular carcinoma group 6 out of 12 cases (50%) were positive for P53 protein and 4 out of 12 cases (33.3%) were positive for P21WAF1 protein. In the follicular adenoma group, 18 out of 57 cases (31.6%) were positive for P53 and 16 out of 57 cases (28.1%) were positive for P21WAF1 protein. No positive cases of P53 or P21WAF1 proteins presence were found in the nodular goiter group. Positive correlation between the expression of P53 and P21WAF1 proteins was found for follicular carcinoma and adenoma groups (p = 0.034 and p = 0.002, respectively). The obtained results demonstrate that simultaneous immunohistochemical detection of P53 and P21WAF1 proteins expression may be useful in determining functional status of P53 protein, helping to interpret expression of P53 protein in thyroid follicular carcinoma cells.

Adenocarcinoma, Follicular↗

PubMed2004

Analysis of P161NK4A protein expression in follicular thyroid tumors.

PI6INK4A (P16) protein expression was analyzed immunohistochemically in archival material derived from 12 cases of follicular thyroid carcinoma, 57 cases of follicular adenoma and 17 cases of nodular goiter. Among follicular carcinomas, 11 out of 12 examined cases (91.7%) were positive for P161NK4A protein. Among follicular adenomas the percentage of immunopositivity was 76.5% (45/57) and among nodular goiter cases it was 19.3% (13/17). Overexpression of P16INK4A protein was found in 66.7% (8/12) of follicular carcinomas and in 19.3% (11/57) of follicular adenomas; the values of this parameter were statistically significantly higher in the follicular carcinoma group (p < 0.005). No P16INK4A protein overexpression was noted in nodular goiter cells. High immunohistochemically-detected expression of P16INK4A protein in follicular thyroid carcinoma cells suggests that the altered expression pattern of P16INK4A protein may disturb the regulatory mechanisms of thyreocyte cell cycle and plays a significant role in the formation of benign neoplasms and their malignant counterparts derived from follicular thyroid cell.

Adenocarcinoma, Follicular↗

PubMed2004

Analysis of nm23-H1 protein immunoreactivity in follicular thyroid tumors.

Immunohistochemical analysis employing a monoclonal antibody nm23-H1 (the antibody against nm-23 protein) was performed on archival material, consisting of 12 cases of follicular thyroid carcinoma (FTC), 57 cases of follicular thyroid adenoma (FTA) and 17 cases of nodular goiter (NG). Both cytoplasmic and nuclear immunoreactions for nm-23H1 were observed in cells of FTCs, FTAs and NGs. In oxyphilic adenomas cytoplasmic staining was observed. Eleven (91.7%) cases of FTC, 55 (98.2%) cases of FTA and 14 (82.4%) cases of NG were found to be positive for nm23-H1 protein. There were no statistically significant differences in the mean percentage values of immunopositive cells between carcinomas and adenomas. A significant increase in the number of cases with high percentage (more than 50) of positive cells was found in both carcinomas (FTCs) and adenomas (FTAs)--mainly microfollicular ones, in comparison with nodular goiter. It can be concluded that highly positive immunoreaction for the nm23-H1 protein in the cells of carcinomas (FTCs) and microfollicular adenomas indicates for a high proliferation rate of these tumors.

Adenocarcinoma, Follicular↗

PubMed2002

A study of thyroglobulin concentration in the thyroid and serum of patients with different thyroid disorders.

Knowledge concerning the structure and quality of thyroglobulin (Tg) has great significance for the better understanding of the pathogenesis of different thyroid diseases. The localization of the Tg gene and studies of its structure by molecular biological techniques make possible precise investigations of its expression. The aim of our study was to evaluate Tg content in the thyroids and Tg concentrations in the serum of 108 patients suffering from benign or malignant thyroid disorders. The method of investigation was isolating total protein from thyroid tissues obtained during surgery and determining Tg content in the thyroid extracts and Tg concentrations in serum. The Tg concentrations in serum and in thyroid protein extracts were evaluated by fluoroimmunometric assay. Statistical analysis was carried out with the help of the computing programmes.

Adolescent↗

PubMed2002

[Adenoid cystic carcinoma--a case report].

A case of adenoid cystic carcinoma located in trachea, primarily wrongly recognized as a thyroid cancer is presented with an update of the literature. The patient underwent surgical treatment (total thyroidectomy, and partial resection of trachea). Histopathological examination found trachea as a primary location of ACC and thyroid tumour as a metastatic one. After operation the patient underwent radiotherapy. Literature review found ACC of trachea as a very rare malignant tumour, and no such a case was presented in the past.

Carcinoma, Adenoid Cystic↗

PubMedDate not supplied

[Medullary thyroid carcinoma: from molecular studies to clinical decision].

The paper is focused on guidelines of practice in inherited medullary thyroid cancer, diagnosed on the basis of DNA analysis. Identification of RET mutation implies further steps of diagnostic procedure, some of them - USG, FNAB and calcitonin level tests - are common for all types of mutation, other are related to ascertained type of mutation. In asymptomatic RET mutation carriers, prophylactic thyroidectomy is indicated. In MEN2B inherited cancer reveals its symptoms quickly and shows dynamic progress. In MEN2A/FMTC the clinical picture is diversified - in some patients the course of disease is mild, however in some other cases the progression of disease and even death occur regardless of the proper treatment. Unfortunately, there are no molecular prognostic markers in medullary thyroid carcinoma. Recent papers and also our own unpublished results show that gene expression profile, is similar in MEN2A and sporadic cancer. This group differs from MEN2B by its expression profile. In conclusion it is to be emphasized that although inherited medullary thyroid carcinoma is a rare disease, the diagnostic algorithm is well established and maximizes the chance for early diagnosis. Moreover, it needs to be stressed that DNA analysis results inform us not only about the necessity of further therapy, but also suggest different ways of proceeding in particular type of mutation.

Carcinoma, Medullary↗

PubMedDate not supplied

[Gene expression analysis by DNA microarray in papillary thyroid cancer].

In our study we present chosen elements of microarray analysis of gene expression profile in papillary thyroid cancer. The study group included 16 papillary thyroid cancer tissues and 16 corresponding normal tissues. Samples were analyzed on high density oligonucleotide microarrays (GeneChip HG-U133A) which contain 22.000 genes. 110 genes, which had significant changed expression, were selected by MAS 5.0 program. 3 genes were chosen to the deeper analysis: dipeptidylpeptidase 4 (DPP4), fibronectin 1 (FN1), tissue inhibitor of metalloproteinase 1 (TIMP1). DPP4-RNA were absent in normal tissue while in cancer tissue it was detected in large amount. FN1 and TIMP1 expression were detected in normal tissue but markedly increased in papillary thyroid cancer. Among these 3 genes DPP4 seems to be the best molecular marker for papillary thyroid cancer.

Adenosine Deaminase↗

PubMedDate not supplied

[Clinical course and treatment of patients with differentiated thyroid carcinoma diagnosed during the year 1995].

The aim of the study was to analyze the clinical course and therapy in patients with differentiated thyroid carcinoma (DTC) diagnosed in Poland within the year 1995. The group of 478 patients with thyroid cancer (57.7% of all thyroid cancer cases diagnosed this year in Poland) was analyzed. Patients were diagnosed or treated in Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch. Detailed analysis was performed in 352 patients with DTC who were treated by surgery. 292 patients (60%) received adjuvant radioiodine therapy. Hormonal (L-thyroxine) treatment was administered to all patients. In 37 patients (8.6%) local recurrence was observed. 10-year overall survival was 96.4% and disease-free survival was respectively 68%. The comparison of Polish data to analysis in German population published by Holtzer et al. (Cancer, 2000) was also performed in this study. We conclude that DTC therapy, currently recommended in our country, gives satisfactory results and that clinical outcome and therapeutic methods are similar both in Poland and Germany.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

[The impact of the extent and time of operation on the survival in patients with differentiated thyroid carcinoma (DTC)].

INTRODUCTION: To analyze the impact of time and extent of operation on overall and disease-free survival in patients with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS: Retrospective analysis of 1235 DTC patients, a representative probe of patients diagnosed or treated between 1986 to 1998 was performed. 277 patients were staged T1M0 and 958 ones staged > T1M0. 10-year outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard model. RESULTS: The T1M0 patients were characterized by the best overall and disease-free survival independently of the time and the extent of operation (98% and 96% respectively); in > T1M0 group the survival was better in patients who were treated by total thyroidectomy (94% and 68% respectively) than in patients treated by non-total thyroidectomy (78% and 47% respectively). In patients treated by completion of total thyroidectomy delayed more than 1 year post cancer diagnosis the incidence of carcinoma in postoperative pathological material was twice as high in comparison to the group in whom total thyroidectomy was performed within the first year of therapy (p = 0.000). CONCLUSIONS: 1. In differentiated thyroid carcinoma the prognosis is related to the extent of operation only in patients staged more than T1M0. 2. A delay > 12 months in completion surgery in patients with differentiated thyroid cancer (tumors > 1 cm of diameter) significantly increases the risk of progression of multifocal disease in thyroid remnants.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

[Completion total thyroidectomy in children with differentiated thyroid cancer].

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

[Evaluation of the therapeutic benefits in relation to the extent of surgery in patients with differentiated thyroid carcinoma].

INTRODUCTION: Evaluation of the therapeutic benefits in relation to the stage of thyroid cancer and to the extent of surgery and the risk of postoperative complications. MATERIAL AND METHODS: Retrospective analysis of differentiated thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of them were treated or diagnosed in Institute of Oncology in Gliwice between 1986-1998. Previously they were operated in various surgical centers all-over Poland. The risk of death, local relapse and postoperative complications were analyzed using the decisiontree model to evaluate the therapeutic benefits. RESULTS: The recurrent laryngeal nerve injury (transient or permanent) was observed in retrospective analysis in 21% of patients, while postoperative hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in patients treated by less than total thyroidectomy). The advantage of radical surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in patients treated by total thyroidectomy and 0.69 in those who received less extensive operation. CONCLUSIONS: The analysis of therapeutic benefits confirmed the limit of 1 cm tumor diameter between less extensive surgery and total thyroidectomy. It showed that total thyroidectomy brings a significant therapeutic benefits in patients in > T1M0 stage. The improvement of overall survival and decrease of local relapse far outweigh the disadvantages related to postoperative complications.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

[Indications for surgery of thyroid cancer based on bioptate molecular examination].

INTRODUCTION: In differentiated thyroid cancer (DTC) the differentiation between reactive and metastatic lymph nodes is difficult at the early stages of metastasis. The aim of the study was to assess the results of fine needle aspiration (FNA) samples examination by the use of RT-PCR for Tg mRNA. The special attention was directed to the evaluation of specificity of TgRNA estimation. MATERIAL AND METHODS: The group consisted of 193 DTC patients with suspicion of lymph node recurrence and at least one positive RT-PCR result. Thyroglobulin RT-PCR was conducted in residual material left after preparation of cytological smears from FNA specimens. Primer spanning exons 3-5 were used with 39 cycles of PCR. RNA isolation control and cDNA amplification were carried out using GAPDH starters. 308 lymph node biopsies were included. RESULTS: 246 positive results for Tg RNA were observed in the analyzed group, 71.1% confirmed by FNA. Among other 71 results, in which cytological examination did not correspond unequivocally to molecular findings, in 34 metastases were confirmed both by cytological and clinical examination. There were 11 patients operated due to the positive serial molecular examination only. In 10 (91%) of them DTC metastases were confirmed. So, the positive predictive value of the molecular result ranged between 75-89% and the negative one was 100%. CONCLUSIONS: In DTC patients RT-PCR Tg mRNA is helpful in qualification of suspicious lymph nodes to surgery in DTC patients. At the negative cytological finding, the positive molecular result constitutes an indication for early surgery.

Adenocarcinoma, Papillary↗

PubMedDate not supplied

[Medullary thyroid carcinoma: the comparison of the hereditary and sporadic types of cancer].

INTRODUCTION: The assessment of frequency and type of mutation and differences in prognosis between sporadic and hereditary type of medullary thyroid carcinoma (MTC), based on own DNA analysis, was performed. MATERIAL AND METHODS: The group of 190 persons with hereditary MTC or asymptomatic mutation carriers was analyzed. Patients with sporadic MTC without RET gene mutation were included into control group (708 persons). The recognition of MTC type was based on assessment of family history, physical examination and genetic analysis. The family history consisted of information about MTC, pheochromocytoma and other neoplasms and hyperparathyroidism in relatives. RESULTS: The mutations located in codon 634 of exon 11 were the most often (43% of all mutations and 49% of mutations in syndrome MEN 2A/FMTC). The age of diagnosis was ranged between 7 and 71 years (mean age: 39 +/- 15.2 years, median age: 41 years). In hereditary MTC the mean age of diagnosis was 27 +/- 13.9 years and was significantly lower than in sporadic one, where it was 45.7 +/- 14.3 years. The relationship between diagnosis, age and subtypes of hereditary MTC was assessed--no significant differences in examined subgroups were observed. The mean age of diagnosis in MEN 2A/FMTC and MEN 2A syndrome was 28-29 years, in MEN 2B - 21 years. The overall survival in sporadic MTC after 5 years was 97%, in hereditary MTC - 79%. Analysis performed after excluding suprarenal causes of death revealed no statistically significant differences in overall survival between both subtypes of MTC. CONCLUSIONS: 1. Hereditary MTC is still diagnosed too late, besides of DNA analysis. 2. In hereditary and sporadic MTC the prognosis is comparable.

Adolescent↗