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To assess the incidence of post-partum thyropathies in women with positive antibodies against thyroid peroxidase in the second trimester of pregnancy.Based on a cross-sectional study of the prevalence of abnormal laboratory parameters of thyroid function in a group of 650 pregnant women in the second trimester of pregnancy the authors invited for subsequent clinical examination and repeated controls women with elevated antibodies against thyroid peroxidase (antiTPO) above 60 mU/l (1). The group comprised 75 pregnant women, incl. 44 (58.7%) who attended the examination. After delivery the authors examined the serum levels of TSH, fT4, antiTPO, if necessary fT3 and TRAK.18, i.e. 58.1% women developed post-partum thyroiditis, incl. 10, i.e. 55.6% who developed hypothyroidism and 8, i.e. 44.4% who developed hyperthyroidism.Based on the presented study the authors recommend in pregnant women in the first trimester of pregnancy to introduce assessment of thyrotropin (TSH) and free thyroxin (fT$) and antibodies against thyroid peroxidase (antiTPO)[to detect neuropsychic sequelae on the infant after delivery. The investigation of serum levels of antiTPO antibodies will make it possible to select a group of women in risk of by the development of post-partum thyropathies which must be followed up.

The aim of this study was to determine the diagnostic capabilities of tumor markers in pleural effusion and their importance for assessment of the etiology of pleural effusions.In pleural effusions from 166 patients hospitalized during the period 2003-2005 at the Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen, the following tumor markers were determined: thymidine kinase (TK), neuron-specific enolase (NSE), cytokeratins [tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 19 (CYFRA 21-1)], carcinoembryonic antigen (CEA) and mucinous markers (CA 15-3, CA 19-9, CA 125). The inflammatory marker procalcitonin-PCT was also assessed.Tumor markers CA 125, TPA, TPS were significantly elevated in exudates, irrespective of the etiology, as a non-specific reaction in mesothelial cells. TK had a sensitivity of over 80% for all the types of cancer examined, while CA 15-3 had a sensitivity of over 90%.Significant positivity of PCT and CA 15-3 in pleural effusions indicate a suspicion of inflammatory disease. Positivity of TK and CA 15-3 indicate a strong suspicion of malignant exudates.

The diagnostics and the treatment of the disorders of the thyroid gland in pregnancy belong to the most important topics for most endocrinologists in the whole world. Untreated or mistreated thyroid gland disorders may influence the course of pregnancy and development of the foetus and child. Autoimmune thyroiditis, hyperthyroidism and hypothyroidism represent the most common thyreopaties in pregnancy and that is why the aim of the study was to establish their prevalence in population of pregnant women of the West Bohemia region. In our study we assessed serum levels of thyrotropin (TSH), free tyroxin (fT4) and antithyroid peroxidase antibodies (antiTPO) in 650 pregnant women. Sera were acquired during routine blood sampling for Down syndrome screening in the 2nd trimester of pregnancy. In our group we found the prevalence of 1.5% of hypothyroidism and 9.4% of autoimmune thyroiditis and we revealed no case of thyrotoxicosis, only subnormal TSH in 2.3%.

The aim of the study was to determine whether VEGF, TPS, TK or Endostatin determination in tissue cytosol may have some additional value in distinguishing among different types of thyroid lesions. These markers were chosen as representatives of the 2 main pathways (angiogenesis and proliferation) involved in thyroid diseases. VEGF is the most potent angiogenic promoter and Endostatin plays an opposing role. Thymidine kinase (TK) is a marker of DNA synthesis and TPS, cytokeratin 18 fragments, is a marker of the rate of proliferation. We determined qualitatively all four markers in tissue extracts: cytosol from 157 tissue specimens (93 goitre, 12 Hashimoto's thyroiditis, 39 adenomas and 13 carcinomas). In 6 cases we were able to compare both normal and pathological tissue samples from a single patient. Statistically significant differences were found in the measured markers, but outliers were present in all groups. This fact does not permit their use in differential diagnosis. The highest levels of all markers were reached in adenomas, being higher than in carcinomas, probably explained by the higher overall metabolic rate in adenomas.

RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a glycoprotein which negatively regulates the activity of matrix metalloproteinases (MMPs). We analyzed differences in RECK mRNA expression in histological types of non-small cell lung cancer (NSCLC) and the relationship between promoter methylation status of RECK gene, level of RECK mRNA expression and clinicopathological values of patients with NSCLC.Methylation status of the promoter and the expression of RECK mRNA were analyzed in paired tissue samples (tumor and control) of 50 patients with NSCLC. The methylation status of the RECK promoter was assessed using methylation-specific PCR. The level of RECK mRNA expression was measured using an RT real-time PCR method.Lower expression of RECK mRNA in NSCLC tissue was recorded compared to normal tissue (p=0.0032). Significantly lower expression of RECK in squamous cell carcinoma (SCC) tissue was observed in comparison with adenocarcinoma tissue (p=0.0051). Significant differences in expression of RECK in stages IB-IIIA were found in comparison with stage IA (p=0.0455). There was a significantly lower expression of RECK mRNA in NSCLC tissue in samples with positive RECK promoter methylation status in comparison with samples with negative promoter methylation status (p=0.0400).We showed that there were differences in expression between histological types of NSCLC (SCC, adenocarcinoma). There was a higher expression of RECK in stage IA in comparison with stages IB-IIIA. Our results indicate that RECK could be classified as a tumor suppressor gene and is an interesting target for further investigation of MMP inhibitors.

Paper deals with detection of the early disease progression in breast cancer patients during follow up using tumor markers.The basic group of 1184 patients with breast carcinoma in follow up after primary therapy were examined from 1996 to 2002. Sera were tested using commercial kits CA 15-3 (MEIA, Abbot), CEA (IRMA, Immunotech), TPA (IRMA, Byk Sangtec), TPS (IRMA, Beki). Results were compared with the retrospectively confirmed clinical status of individual patients. The authors calculated optimal cut offs and sensitivities and their combinations for particular tumor markers at 95% level of specificity. Best sensitivities for the detection of distant metastases into bone, liver, lung and brain was achieved by CA 15-3 (53-68%). As an optimal combination of tumor markers seems to be the tricombination CA 15-3, CEA and TPA. All the tumor markers have insufficient sensitivity for the metastatic process into the lymphnodes.As optimal combination of tumor markers during the follow up seem to be tricombination CA 15-3, CEA and TPA, but also the clinical relevance and cost effectiveness of these assessments have to be considered. For the tumor disease follow up only CA 15-3 has sufficient sensitivities (at 95% specificities) for the early diagnosis of the metastatic process.

Circulating cytokeratins have shown to be important for management of patients with lung cancer. Here we investigated their role for differential diagnosis, therapy monitoring and prognosis in colorectal cancer (CRC).Pretherapeutic levels of cytokeratin-19 fragments (CYFRA 21-1), carcino-embryonic antigen (CEA) and cancer antigen (CA) 19-9 were measured in 42 patients with CRC, 45 with benign colorectal diseases and 51 healthy controls. Furthermore, courses of CYFRA 21-1, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), M30-antigen, CEA and CA 19-9 were analyzed in prospectively collected sera of 15 patients with CRC during primary chemotherapy and were correlated with therapy response and overall survival (OS).Similar to CEA and CA 19-9, CYFRA 21-1 was significantly elevated in serum from patients with CRC (median 2.1 ng/ml) as compared with healthy (1.2 ng/ml; p0.0001) and benign gastrointestinal controls (1.7 ng/ml; p=0.0178) and showed stage dependency in CRC (p=0.0118). CYFRA 21-1 correlated with CEA in benign diseases and CRC but not with CA 19-9. The best discrimination between healthy controls and patients with CRC was achieved by combination of CYFRA 21-1 and CA 19-9 (area under the curve; AUC=86.7%), while the combination of CEA and CA 19-9 discriminated best between benign diseases and CRC (AUC=73.9%). In CRC patients during primary chemotherapy, levels of cytokeratins CYFRA 21-1, TPA, TPS, CEA and CA 19-9 tended to be higher in patients with poor response to therapy and with poor prognosis.Cytokeratins are elevated in patients with CRC and show some association with response to primary therapy and prognosis.

The authors present the view of possible usage of tumour markers in epithelial ovarian cancer, and they aim at their use in routine clinic practice.Review article.Oncology and Radio-Therapeutic Department, Faculty Hospital, Pilsen. SUBJECT AND METHODS OF THE STUDY: Summary of data published in Czech and foreign professional literature.In case of epithelium tumours of ovaries, CA 125 is the tumour marker of the first choice. For the reason of low sensitivity, it is not possible to use the tumor markers for screening and primary diagnostics. Regarding prognoses, high pre-operational levels of CA 125 are considered unfavourable. At the same time the study demonstrates that CA 125 levels monitoring in the course of chemotherapy appears to be one of the most significant indicators of chemotherapy effects and, therefore, also of prognoses. Regular CA 125 monitoring in the course of follow up can contribute to early detection of tumour disease relapses. The optimal time interval for monitoring seems to be three months for the period of the first two years, and then six-month interval. Other tumour markers used in routine clinic practice are mainly CA 19-9 and CA 72-4, particularly in case of mucinoid epithelium tumours. However, these markers are of subsidiary importance only.

Early diagnosis of prostate cancer (PCa) in an organ-confined stage following radical treatment is the only potential curative approach in PCa. Prostatic-specific antigen (PSA) is very helpful in early diagnosis, but the main disadvantage is that it has a low positive predictive value in the range of the grey zone of 2.5-10 ng/mL, which results in a high number of needless biopsies. For this reason, new tests with better parameters are needed. One promising test is that for differential display code 3 (DD3(PCA3)), which is a prostate-specific non-coding mRNA that is highly overexpressed in prostate tumor cells. The aim of the present study was to evaluate the potential of DD3(PCA3) for mRNA in PCa diagnosis.A total of 186 patients were examined. In a group of patients with suspected PCa, one tissue specimen core was collected for testing DD3(PCA3) expression. According to the histological verification there were 100 patients with benign prostatic hyperplasia, 12 patients with prostatic intraepithelial neoplasia and 74 patients with PCa. The total RNA was isolated and DD3(PCA3) and PSA expressions were quantified using quantitative RT real-time PCR method. The DD3(PCA3)/PSA mRNA ratio was determined for all groups.It was found that the levels of the mRNA expression of DD3(PCA3) were significantly higher (p0.045) in patients with PCa than in patients with benign prostatic hyperplasia. No statistically significant differences in levels of mRNA expression of DD3(PCA3) between patients with organ-confined and those with advanced or metastatic disease, nor according to Gleason score, were found.DD3(PCA3) appears to be a promising marker for early detection of PCa and also for differential diagnosis between patients with benign prostate hyperplasia and those with PCa.

The trend of current research is not only to obtain a complete characterisation of the cause of inception of tumor proliferation, but in particular to characterize in detail multi-degree cascades of the metastatic process. Precise description of the effector genes and their protein products which influence individual processes of the metastatic cascade, is of great significance not only for the early diagnosis of the possible tumor invasion into its immediate environment and the creation of distant metastases, but particularly for the development of new therapeutic procedures which will help to change from empirical to causal treatment. In practice this means a shift from those therapeutic procedures which lead only to simple blocking of cell division or cell growth, to addressing the individual stages of tumor development (correction of genetic defects in tumor cells, inhibition of the metastatic cascade, inhibition of angiogenesis and apoptosis, etc.). The article characterizes the biological activity of tumors in connection with the metastatic process in colorectal carcinoma.

Examination of tumour markers conducive to follow up of the patients with colorectal carcinoma.The tumour markers were examined in the population of patients with primarily established and histologically verified colorectal adenocarcinoma.The resection therapy resulted in the decrease in post-operative CEA levels. There were no changes in pre- and post-operative CA 19-9 levels; unlike with post-operative TPS levels having been significantly increased, probably due to reparation processes resulting from the surgery. It can be concluded that pre- and post-operative CEA levels are the most suitable markers to check the effect of surgery. With a 95%-specificity for the establishment of recidives, the highest sensitivity was reached with TPS (83%); the sensitivities of the classical tumour markers CEA and CA 19-9 were significantly lower (41% and 25%, respectively). The results should be interpreted with caution due to a small number of relapses regarding a short follow up and rather local-regional character of the recidives.However, TPS seems to be a promising marker for the follow up of the patients with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and TPS.

Tumor markers are used for the prediction of relapse and in determining the effect of postoperative or post-oncological therapy as a standard component of follow-up. Metastatic processes of the liver and primary malignancies of the liver and gall bladder are very common in the European population. The aim of this study was to demonstrate the behaviour of malignancy in patients who have not undergone surgical therapy and to study serum levels of the monitored tumor markers in relation to the life expectancy of these patients.The Log-rank test and Wilcoxon test were used for statistical evaluation. Survival was computed using the Kaplan-Meier method. Serum levels of the tumor markers conventionally used in clinical practice in patients with gastrointestinal tumors (CEA, CA19-9, C724) and the markers of the proliferation activity in malignancy (TK, TPA, TPS) were studied.One hundred and nine patients who underwent exploratory laparotomy without any surgical therapy between September 1999 and June 2005 were studied. For patients with a serum level of CEA, CA19-9 and CA72-4 that was higher than the calculated cut-off hazard ratios of early death were respectively 3-, 5- and 9-fold higher than for patients with serum levels of the same tumor markers below the calculated cut-off. Preoperative serum levels of proliferative tumor markers (TK, TPA and TPS) were not statistically significant for the prediction of early death.The results of the pilot study suggest the importance of tumor markers for the prediction of the short-term survival rate. These markers could be used to supplement classic clinical, laboratory and radiodiagnostic parameters. It would be very helpful for the planning of palliative oncological therapy for patients with liver malignancies who cannot be treated by surgical therapy.

According to previous reports in the literature, the T790M mutation indicates an acquired resistance to tyrosine kinase inhibitors. The initial positive effect of combination chemotherapy with erlotinib as the first line of treatment correlates with several positive predictors including the type of carcinoma, non-smoking status, occurrence of rash and the presence of exon 19 EGFR gene mutation. The case of a 32-year-old, non-smoker with non-contributory history patient, who was diagnosed with adenocarcinoma in the left lung T4N0M0 stage IIIB is reported. The patient underwent 6 cycles of chemotherapy with erlotinib, gemcitabine and cisplatin, followed by complete remission. Fifteen months after commencing therapy, disease recurred over subsequent therapy with erlotinib and then gefitinib. During that time, bone and cerebral metastases with pericardial effusion were detected. The patient died 7 months later. Genetic examination of tumour tissue collected at the beginning of therapy revealed activating exon 19 mutation in the EGFR gene. Later, during the relapse, the same mutation was still present and, in addition, a T790M mutation in exon 20 of EGFR was found. The subsequently acquired resistance against both erlotinib, as well as gefitinib was most likely a result of tumor cells acquiring the T790M mutations and escaping the drug effect. The authors recommend testing for T790M mutation presence in selected patients prior to targeted therapy with tyrosine kinase inhibitors.

The authors present a statistical analysis of the dynamics of tumour markers and compare these with single serum levels in patients before and after liver surgery for colorectal liver metastases (CLM).The serum levels of tumor markers conventionally used in clinical practice (CA19-9, CEA, CA72-4) and markers informing of the proliferation activity of malignancy (TKI TPA, TPS) were statistically analysed. The authors studied 144 patients who underwent liver surgery for colorectal liver metastases between September 1999 and June 2005. Serum levels of tumor markers before surgery (maximally two weeks before the operation), after surgery (maximally one month after the operation - usually on the day of dismission), six months (+/- one month) and twelve months after the surgery (+/- one month) were determined. The Log Rank test and the Wilcoxon test were used for statistical evaluation. The survival rate and disease-free intervals (DFI) were computed using the Kaplan-Meier method.The statistical analysis of tumour marker dynamic after liver surgery (speed and power of recurrence) supported the dynamics of CA 19-9 and CEA as excellent prognostic factors of early recurrence of CLM in contrast to proliferative tumor markers.The results of the study suggest the importance of tumour markers for the prediction of a short survival rate or DFI. This approach would be very helpful for the planning of palliative oncological treatment for patients with liver malignancies that cannot be treated by surgical therapy. Current patients with a high tendency of recurrence of CLM after liver surgery should be followed up more thoroughly to increase the possibility of successful reoperation.

MicroRNAs (miRNAs), which are endogenously expressed regulatory noncoding RNAs, have an altered expression in tumor tissues. MiRNAs regulate cancer-related processes such as cell growth and tissue differentiation, and therefore, might function as oncogenes or tumor-suppressor genes. The aim of our study was to assess the expression of mir-20a, let-7a, miR-15a and miR-16 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) tissue and to investigate the relation between the expression of miRNAs and the clinicopathological features of PCa.The study group comprised 138 patients: 85 patients with BPH and 53 patients with PCa. The total RNA was isolated from the tissue specimen core and miRNA expressions were quantified using a real-time RT-PCR method (TaqMan MicroRNA Assays). U6snRNA was used for the normalization of the miRNA expression.miR-20a expression was significantly higher in the group of patients with a Gleason score of 7-10 in comparison with the group of patients with a Gleason score of 0-6 (p=0.0082). We found no statistical differences in the miRNA expressions (mir-20a, let-7a, miR-15a and miR-16) in the PCa tissue samples in comparison with the BPH tissue samples.Our result shows that the more dedifferentiated PCa cells have a higher expression of miR-20a and this supports the oncogenic role of miR-20a in PCa carcinogenesis. The evaluation of miRNA expression could yield new information about PCa pathogenesis.