BACKGROUND/AIM: Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis. PATIENTS AND METHODS: This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival. RESULTS: Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413. CONCLUSION: The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.

• MeSH
• antigen CA-19-9 * krev   MeSH
• antigeny nádorové krev   MeSH
• dospělí MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• karcinoembryonální antigen * krev   MeSH
• keratin-19 krev   MeSH
• keratiny krev   MeSH
• kolorektální nádory * krev   diagnóza   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * krev   MeSH
• peptidy MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thymidinkináza * krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• diagnostické techniky molekulární metody   MeSH
• keratin-19 MeSH
• kohortové studie MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické metastázy diagnóza   MeSH
• mastektomie MeSH
• nádory prsu * chirurgie   diagnóza   MeSH
• stupeň nádoru MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

AIM: To investigate potential associations between selected oncomarkers [carcinoembryonic antigen (CEA), C-terminus of cytokeratin 19 (CYFRA 21-1, CYFRA), and squamous cell carcinoma antigen (SCC)] and outcomes in patients with NSCLC treated with bevacizumab plus chemotherapy. PATIENTS AND METHODS: We retrospectively analysed 105 patients with NSCLC from the Czech TULUNG registry treated at University Hospital in Pilsen with bevacizumab plus chemotherapy. Response to therapy was tested by Fisher's exact test. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: Only normal values of CYFRA (not CEA or SCC) were associated with significantly better overall and progression-free survival in univariate analysis. We also observed a trend for a better disease control rate in patients with normal levels of CYFRA. In a multivariate Cox model, only CYFRA was associated with significantly better overall but not progression-free survival. CONCLUSION: In our retrospective study, we point out the possibility of using CYFRA as a prognostic marker in patients with NSCLC treated with chemotherapy plus bevacizumab.

• MeSH
• antigeny nádorové analýza   krev   fyziologie   MeSH
• bevacizumab aplikace a dávkování   škodlivé účinky   MeSH
• biomarkery farmakologické analýza   MeSH
• karcinoembryonální antigen analýza   krev   MeSH
• keratin-19 analýza   krev   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   fyziologie   MeSH
• nádory plic diagnóza   farmakoterapie   mortalita   patologie   MeSH
• nemalobuněčný karcinom plic diagnóza   farmakoterapie   mortalita   patologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• serpiny analýza   krev   MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Thyroid cytology is a widely accepted tool in the clinical triaging of nodular lesions. Cell blocks (CBs) can help in the diagnosis of atypical lesions, namely, thyroid Bethesda category of Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). METHODS: In a series of 224 AUS/FLUS thyroid samples with CB, we studied CB cellularity and feasibility of 3 immunohistochemical markers (cytokeratin 19 [CK19], HBME-1, and galectin-3) apart and in combination. RESULTS: The CBs were non-diagnostic in 34 cases. Twenty-four CBs contained <10 cells, 45 CBs 10-50 cells, and 121 CBs >50 cells. Notably, more cellularity was found in CBs performed by plasma-thrombin and in-house techniques (p < 0.001). The diagnostic accuracy to detect malignancy was 65.1% for CK19, 72.1% for HBME-1, and 70.3% for galectin-3. CONCLUSION: In conclusion, CB cellularity is essential for successful immunohistochemistry application and further diagnostic workup of AUS/FLUS cases.

• MeSH
• fixace tkání MeSH
• galektiny analýza   MeSH
• imunohistochemie * MeSH
• keratin-19 analýza   MeSH
• krevní proteiny analýza   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory štítné žlázy chemie   patologie   MeSH
• prediktivní hodnota testů MeSH
• reprodukovatelnost výsledků MeSH
• retrospektivní studie MeSH
• studie proveditelnosti MeSH
• stupeň nádoru MeSH
• zalévání tkání do parafínu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The aim of the study was to compare the prognostic significance of lymph node status of patients with lung cancer analyzed by three different methods: hematoxylin and eosin (H&E), immunohistochemistry of cytokeratin 19 (IHC CK19), and One-Step Nucleic Acid Amplification (OSNA). The clinical relevance of the results was evaluated based on relation to prognosis; the disease-free interval (DFI) and overall survival (OS) were analyzed. During radical surgical treatment, a total of 1426 lymph nodes were obtained from 100 patients, creating 472 groups of nodes (4-5 groups per patient) and examined by H&E, IHC CK19 and OSNA. The median follow-up was 44 months. Concordant results on the lymph node status of the H&E, IHC CK19 and OSNA examinations were reported in 78% of patients. We recorded shorter OS in patients with positive results provided by both OSNA and H&E. The study demonstrated a higher percentage of detected micrometastases in lymph nodes by the OSNA method. However, the higher sensitivity of the OSNA, with the cut-off value 250 copies of mRNA of CK19/μL, resulted in a lower association of OSNA positivity with progress of the disease compared to H&E. Increasing the cut-off to 615 copies resulted in an increase in concordance between the OSNA and H&E, which means that the higher cut-off is more relevant in the case of lung tumors.

• MeSH
• imunohistochemie metody   MeSH
• keratin-19 genetika   MeSH
• lidé MeSH
• lymfatické metastázy * MeSH
• lymfatické uzliny patologie   MeSH
• metastázy nádorů MeSH
• nádorové biomarkery genetika   MeSH
• nádory plic diagnóza   patologie   chirurgie   MeSH
• následné studie MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• prospektivní studie MeSH
• staging nádorů MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND AND OBJECTIVES: Utilisation of the one-step nucleic acid amplification (OSNA) molecular biology method for the detection of the metastatic involvement of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients. A comparison with histopathological ultrastaging and a description of the clinical consequences. METHODS: Surgically treated EC patients underwent detection of SLNs. Nodes greater than 5 mm were cut into sections 2-mm thick parallel to the short axis of the node. Odd sections were examined according to the OSNA method, while even ones according to an appropriate ultrastaging protocol. Nodes less than or equal to 5 mm were cut into halves along the longitudinal axis with one half examined according to the OSNA method and the other half by ultrastaging. RESULTS: Fifty-eight patients were included and 135 SLNs were acquired. Both ultrastaging and OSNA agreed on 116 results. According to the OSNA method, 20.69% more patients were classified into International Federation of Gynecology and Obstetrics (FIGO) stage III. When comparing the results of the OSNA method to the conclusions of ultrastaging as a reference method, sensitivity of 90.9%, specificity of 85.5% and concordance of 85.9% were attained. CONCLUSIONS: The results of the OSNA method showed a higher frequency of detection of micrometastases and included 20.69% more patients into FIGO stage III.

• MeSH
• adenokarcinom z jasných buněk genetika   sekundární   chirurgie   MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• dospělí MeSH
• keratin-19 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• mikrometastázy MeSH
• míra přežití MeSH
• nádorové biomarkery genetika   MeSH
• nádory endometria genetika   patologie   chirurgie   MeSH
• následné studie MeSH
• nukleové kyseliny analýza   genetika   MeSH
• peroperační doba MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sentinelová uzlina patologie   chirurgie   MeSH
• serózní cystadenokarcinom genetika   sekundární   chirurgie   MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND/AIM: The aim of this study was to analyze the pretreatment cytokeratin serum levels in head and neck squamous cell carcinoma (HNSCC) by three assays in relation to selected clinicopathological characteristics in an effort to find diagnostic/prognostic biomarkers for HNSCC and determine the best assay. PATIENTS AND METHODS: In total, 46 patients with HNSCC with different subsite (oropharyngeal-21 cases, hypopharyngeal-4 and laryngeal-21) were included in this prospective study. MonoTotal, Cyfra 21-1, and TPS radioimmunoassay kits were used to analyze cytokeratin fragments serum levels. RESULTS: Statistically significant differences in serum levels of TPS and Cyfra 21-1 were found between low (stage I-II)- and high-stage (stage III-IV) tumors (p=0.0057; p=0.0138 respectively). Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors. CONCLUSION: The present study is the first to compare cytokeratin serum levels between various subgroups of HNSCC using three different assays. Cyfra 21-1 seems to be the most useful for clinical practice. The relation between elevated Cyfra 21-1 serum levels and p16 expression requires further investigation.

• MeSH
• antigeny nádorové krev   MeSH
• dlaždicobuněčné karcinomy hlavy a krku krev   diagnóza   mortalita   terapie   MeSH
• keratin-19 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové biomarkery * MeSH
• peptidy krev   MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Cílem práce je porovnání senzitivity detekce mikrometastáz v hilových a mediastinálních lymfatických uzlinách primárních (nemalobuněčných) a sekundárních (metastázy kolorektálního karcinomu) nádorů plic pomocí standardního histopatologického vyšetření v barvení hematoxylin- eosin, imunohistochemického vyšetření s protilátkou proti cytokeratinu 19 a metodou One-Step Nucleic Acid Amplification. Metoda: Při radikální chirurgické léčbě nemalobuněčných primárních plicních karcinomů a metastáz kolorektálního karcinomu byly u 100 pacientů zařazených do studie v období 2015–2017 podle standardního schématu odebrány hilové a mediastinální lymfatické uzliny. Tyto uzliny pak byly v podélné ose děleny na 4 stejné části, přičemž část první a třetí zleva byla určena k vyšetření metodou One-Step Nucleic Acid Amplifi cation, část druhá a čtvrtá k histologickému vyšetření. Při histologickém vyšetření byly příslušné části uzlin nejprve vyšetřeny standardním postupem v barvení hematoxylin-eosin a následně pak i imunohistochemicky s protilátkou proti cytokeratinu 19. Metoda One-Step Nucleic Acid Amplification byla prováděna soupravou firmy Sysmex (Kobe, Japonsko), jejím principem je detekce mRNA (messenger ribonucleic acid) cytokeratinu 19 reverzní transkripcí spojenou s izotermickou amplifikací. Výsledky: Celkem bylo nemocným zařazeným do studie odebráno a uvedenou metodikou vyšetřeno 1426 lymfatických uzlin. Shodné výsledky vyšetření hematoxylinem-eosinem, imunohistochemií s protilátkou proti cytokeratinu 19 a One-Step Nucleic Acid Amplification byly zaznamenány u 78 nemocných (78 %). Mikrometastázy v lymfatických uzlinách byly metodou One-Step Nucleic Acid Amplification při negativitě ostatních metod prokázány u 16 pacientů (16 %). Pouze ve 3 případech (3 %) bylo vyšetření hematoxylinem-eosinem, resp. imunohistochemií s protilátkou proti cytokeratinu 19 pozitivní při negativitě metody One-Step Nucleic Acid Amplification. Výsledky imunohistochemie s protilátkou proti cytokeratinu 19 prakticky přesně kopírovaly výsledky vyšetření hematoxylinem-eosinem (97 %). Závěr: Výsledky studie prokázaly vyšší procento detekovaných mikrometastáz v hilových a mediastinálních lymfatických uzlinách při vyšetření metodou One-Step Nucleic Acid Amplification ve srovnání s hematoxylinem-eosinem a imunohistochemií s protilátkou proti cytokeratinu 19 (upstaging 16 %). Ukazuje se tak, že vyšetření lymfatických uzlin pomocí metody One-Step Nucleic Acid Amplifi cation může mít určitý potenciál zpřesnit staging plicních nádorů, naopak imunohistochemie s protilátkou proti cytokeratinu 19 změny stagingu téměř nepřináší. Je však nezbytné potvrdit tento předpoklad v dalších studiích, resp. na větším souboru nemocných. Dalším úkolem je také pečlivým sledováním nemocných zjistit souvislost mikrometastáz detekovaných v lymfatických uzlinách metodou One-Step Nucleic Acid Amplification s jejich follow-up.

Introduction: The aim of this article is to compare the sensitivity of detecting micrometastases in hilar and mediastinal lymph nodes in case of primary (non-small cell) and secondary (metastases of colorectal carcinoma) pulmonary tumours using standard histopathological examination with haematoxylin-eosin staining, immunohistochemistry examination with Anti-Cytokeratin 19 antibody and examination based on the One-Step Nucleic Acid Amplification method. Method: During radical surgical treatment of primary non-small cell lung carcinoma and pulmonary metastases of colorectal carcinoma, hilar and mediastinal lymph nodes of 100 patients enrolled in the study in the period from 2015 to 2017 were extracted based on a standard classifi cation. These lymph nodes were subsequently divided along the longitudinal axis into 4 identical parts where part one and three on the left were intended for examination based on the One-Step Nucleic Acid Amplification method, whereas parts two and four were subjected to histopathological examination. In evaluating the respective parts of the nodes by histological examination, the nodes were fi rst examined by a standard procedure that involves haematoxylin-eosin staining, followed by immunohistochemistry examination with Anti-Cytokeratin 19 antibody. The One-Step Nucleic Acid Amplification method was performed in the kit supplied by Sysmex (Kobe, Japan) and is based on the detection of cytokeratin 19 mRNA (messenger ribonucleic acid) by reverse transcription coupled with isothermal amplifi cation. Results: A total of 1,426 lymph nodes of the patients enrolled in the study were extracted and examined using the above mentioned methodology. In 78 patients (78%), identical results were obtained using haematoxylin-eosin staining, immunohistochemistry with Anti-Cytokeratin 19 and One- Step Nucleic Acid Amplifi cation. Micrometastases in the lymph nodes using the One-Step Nucleic Acid Amplifi cation method in the absence of the other methods were proven in 16 patients (16%). Only in 3 cases (3%), the examination by haematoxylin-eosin staining, or immunohistochemistry with Anti-Cytokeratin 19, was positive while One-Step Nucleic Acid Amplification was negative. The results obtained by immunohistochemistry with Anti-Cytokeratin 19 antibody were practically the same as those obtained by haematoxylin-eosin staining (97%). Conclusion: The results of the study have demonstrated a higher percentage of metastases detected in hilar and mediastinal lymph nodes if the One-Step Nucleic Acid Amplification method of examination was used compared to haematoxylin-eosin staining and immunohistochemistry with Anti-Cytokeratin 19 antibody (upstaging in 16%). This shows that the examination of lymph nodes using the One-Step Nucleic Acid Amplification method can have a certain potential to make the pulmonary tumours staging more accurate. On the other hand, immunohistochemistry with Anti- Cytokeratin 19 antibody seems to be not so useful. However, it is necessary to prove this hypothesis in follow-up studies, or where applicable, in a larger cohort of patients. Another task is to ascertain, by careful patient monitoring, the infl uence of the micrometastases detected in their lymph nodes using the One-Step Nucleic Acid Amplification method on these patients’ follow-up.

• MeSH
• barvení a značení MeSH
• hematoxylin terapeutické užití   MeSH
• imunohistochemie MeSH
• keratin-19 terapeutické užití   MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické uzliny * anatomie a histologie   diagnostické zobrazování   MeSH
• metastázy nádorů diagnóza   terapie   MeSH
• nádory plic * diagnóza   chirurgie   MeSH
• prospektivní studie MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND/AIM: The results of surgical treatment of breast cancer liver metastases (BCLM) remain suboptimal. The search for perioperative prognostic factors could help determine high risk groups of patients. The aim of study was to evaluate the significance of tumour markers (TM) on long-term treatment results. PATIENTS AND METHODS: Liver surgery was carried out in 32 women for BCLM. The perioperative serum levels of CEA, CA19-9, TPA, TPS, CYFRA 21-1 and TK were determined. RESULTS: Preoperative levels of CA19-9 were significant for overall survival (OS)(p<0.05) and recurrence-free survival (RFS) (p<0.01). TPA, TPS and CYFRA 21-1 levels were significant for OS (p<0.05; p<0.04; p<0.05). Postoperative levels of CEA, TPS and CYFRA 21-1 were significant for RFS (p<0.04; p<0.01; p<0.02), while CA19-9 postoperative levels were significant for OS and RFS (p<0.03; p<0.01). CONCLUSION: Perioperative TM serum levels may represent prognostic indicators reflecting the results of surgical treatment of BCLM.

• MeSH
• analýza přežití MeSH
• antigen CA-19-9 krev   MeSH
• antigeny nádorové krev   MeSH
• dospělí MeSH
• karcinoembryonální antigen krev   MeSH
• keratin-19 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory jater sekundární   chirurgie   MeSH
• nádory prsu patologie   chirurgie   MeSH
• peptidy krev   MeSH
• perioperační období * MeSH
• prognóza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Herbal medicines have been increasingly used in the last three decades. Despite their popularity, safety issues with herbal products need to be addressed. We performed a feasibility study of the toxic responses of human induced pluripotent stem cell-derived hepatocytes (iHep cells) to phytochemicals in comparison with hepatoblasoma-derived HepG2 cells and long-term human hepatocytes (LTHHs). The iHep cells expressed typical hepatocyte markers cytochrome P450 3A4 (CYP3A4), hepatocyte nuclear factor 4α, and albumin despite the expression of immature markers α-fetoprotein and cytokeratin 19. We studied the responses of iHep cells to phytochemicals saikosaponin D, triptolide, deoxycalyciphylline B, and monocrotaline with different mode of toxicity employing MTS and lactate dehydrogenase (LDH) assays. Saikosaponin D and triptolide caused dose-dependent cytotoxicity in the iHep cells, which were more sensitive than LTHHs and HepG2 cells. Saikosaponin D-induced cytotoxicity tightly correlated with increased LDH leakage in the iHep cells. Although deoxycalyciphylline B did not exhibit toxic effect on the iHep and HepG2 cells when compared with LTHHs, it decreased CYP3A7 expression in the iHep cells and increased CYP1A2 expression in HepG2 cells. We hereby show the feasibility of using iHep cells to detect toxic effects of phytochemicals.

• MeSH
• albuminy metabolismus   MeSH
• alfa-fetoproteiny metabolismus   MeSH
• dospělí MeSH
• fytonutrienty toxicita   MeSH
• hepatocytární jaderný faktor 4 metabolismus   MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• indukované pluripotentní kmenové buňky cytologie   MeSH
• keratin-19 metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladiství MeSH
• studie proveditelnosti MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH