BACKGROUND: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology, and both exhibit population heterogeneity. MUC16 is overexpressed in various cancers and often associated with poor prognosis. Present work was to investigate the clinical significance of MUC16 in non-small cell lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution caused by coal use. METHODS: Clinicopathologic characteristics and MUC16 expression were analyzed and evaluated in our subject population. Vectors were constructed for MUC16 gene knockout and overexpression, then we examined how MUC16 affected lung cancer cell behaviors, including proliferation, migration, invasion and chemoresistance. RESULTS: FLC showed significant association with early-onset (P<0.01) and later stage (P<0.01). Indoor air pollution was associated with younger age (P<0.01), later stage (P<0.05) and AD histology type (P<0.05). Interestingly, two age peaks were observed in our FLC and sporadic group respectively, possibly suggesting multiple major contributors to lung cancer in our subject population. MUC16 overexpression was significantly associated with FLC (P<0.05), indoor air pollution (P<0.01) and later stage (P<0.01), additionally more metastasis cases were observed in patients with up-regulated MUC16 (18.1% vs. 10.3%). Taken together, elevated MUC16 may potentially be one molecular character of FLC in local residents. Intriguingly, patients with more MUC16 up-regulation seemed to have a lower number of white blood cells, especially neutrophils, this reflected MUC16's role in immune regulation. In cell behavior experiments, high MUC16 level could contribute to lung cancer cell proliferation, migration, invasion and chemoresistance, but there were variations among cell lines. CONCLUSIONS: MUC16 plays crucial roles in lung cancer pathogenesis, progression and chemoresistance. Interestingly, its association with FLC and indoor air pollution highlights the complexity of lung cancer etiology. Our findings provide useful information to study the intricate interaction between environmental carcinogens and population genetic background.

• Klíčová slova
• Indoor air pollution, MUC16, chemoresistance, familial lung cancer (FLC),
• Publikační typ
• časopisecké články MeSH

AIM: The first aim of the project was to evaluate the benefits of the determination of human epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) index for primary detection of ovarian cancer in a population of Czech women. The second aim was to study the advantages HE4, cancer antigen 125 (CA125) and ROMA index for distinguishing between benign and malignant tumors. Aware of the age distribution of ovarian cancer, we focused on postmenopausal patients. PATIENTS AND METHODS: Our group of patients consisted of 256 females, 21 with ovarian cancer and 235 with benign ovarian tumors. All diagnoses were histologically verified. We determined the serum levels of HE4 and CA125 and calculated the ROMA2 index for postmenopausal women. Serum levels of the analytes were measured using an Architect 1000i instrument. Serum samples were collected prior to surgery or any other form of treatment and the results of the two groups of patients were compared (malignant vs. benign). RESULTS: There was a significant difference in the serum levels for all parameters studied between the groups of patients with malignant and those with benign diagnoses (Wilcoxon test, p<0.0001). When all parameters were evaluated at 95% specificity, the HE4 cut-off was 112 pmol/l at a sensitivity of 71.42%, a positive predictive value (PPV) of 55.56%, a negative predictive value (NPV) of 97.14% and an area under the curve (AUC) of 0.9152. The CA125 cut-off was 81 IU/l at a sensitivity of 80.95%, a PPV of 58.62%, a NPV of 98.23% and an AUC of 0.9731. ROMA2 index had a cut-off 37.70% at a sensitivity of 85.71%, a PPV of 62.06%, a NPV of 98.65% and an AUC of 0.9803. The highest diagnostic efficiency was achieved by the ROMA2 index. CONCLUSION: Determination of HE4 along with CA125 and ROMA2 index calculation is a suitable method for the improvement of the primary detection of ovarian cancer. This approach also improves the differential diagnostic possibilities for distinguishing between malignant and benign tumors.

• MeSH
• algoritmy MeSH
• antigen CA-125 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny krev   MeSH
• nádory vaječníků krev   MeSH
• nemoci ovaria krev   MeSH
• postmenopauza krev   MeSH
• protein WFDC2 MeSH
• proteiny metabolismus   MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč
• protein WFDC2 MeSH
• proteiny MeSH
• WFDC2 protein, human MeSH Prohlížeč

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.

• MeSH
• antigen CA-125 krev   MeSH
• dospělí MeSH
• hodnocení rizik metody   MeSH
• kalibrace MeSH
• konzervativní terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely * MeSH
• membránové proteiny krev   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory vaječníků diagnóza   patologie   terapie   MeSH
• nádory vejcovodů diagnóza   patologie   terapie   MeSH
• ovarektomie MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ultrasonografie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• validační studie MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč

OBJECTIVE: Verification of the importance of determination of HE4 and calculation of ROMA index for increasing the efficiency of diagnosis of ovarian cancer in a population of Czech women. DESIGN: Prospective study. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital in Pilsen. METHODS: In the period from 06/24/2010 to 12/01/2011 was at the Department of Gynaecology and Obstetrics, University Hospital Pilsen examined 552 patients with abnormalities in the pelvis. Patients were divided into two groups. There were 30 women with histologically confirmed malignant ovarian tumors. Another 522 women had benign findings. According to the levels of FSH were women in both groups divided into premenopausal and postmenopausal. At all women were measured CA 125, HE4 and FSH. HE4 and CA125 were determined using the chemiluminescent device Architect 1000 (Abbott, USA), FSH chemiluminescent method on the device DXI 800 (Beckman Coulter, USA). At all premenopausal women was calculated ROMA1 index and at all postmenopausal women ROMA2 index. SAS statistical software 9.2 were used for all statistical calculations. RESULTS: The highest diagnostic efficiency was achieved by a combination of HE4 and CA125 markers with the calculation ROMA2 index for postmenopausal women. In determining of menopausal status according to the values of FSH cut-off for menopause 40 IU/L and cut-off at 26.4% for ROMA2 reaches ROMA2 sensitivity of 92.3%, specificity of 88.5% and PV- of 99.3%. If we reduce the cut-off for laboratory diagnosis of menopause using FSH at 22 IU/L, and cut-off for ROMA2 was 26.3% reaches ROMA2 sensitivity of 95.2%, specificity of 87.8% and PV- of 99.5%. CONCLUSION: HE4 in combination with CA125 and current ROMA index calculation is a suitable methodology to improve the detection of ovarian cancer.

• MeSH
• antigen CA-125 krev   MeSH
• lidé MeSH
• membránové proteiny krev   MeSH
• nádorové biomarkery krev   MeSH
• nádory vaječníků diagnóza   MeSH
• prediktivní hodnota testů MeSH
• protein WFDC2 MeSH
• proteiny analýza   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein WFDC2 MeSH
• proteiny MeSH
• WFDC2 protein, human MeSH Prohlížeč

AIM: An optimal surgical staging in the group of patients with the high-risk type of endometrial cancer is often limited by age and serious internal comorbidities. Therefore, in this study we focused on human epididymis protein 4 and its contribution to the preoperative differentiation of prognostically distinct groups of patients and to individualized surgical treatment as compared with cancer antigen (CA) 125 and imaging methods. MATERIAL AND METHODS: The study included 115 patients with endometrioid adenocarcinoma diagnosed through endometrial biopsy. Before the final operation, blood sampling was performed for the determination of human epididymis protein 4 (HE4) and CA125 levels. Serum levels of both biomarkers were analyzed in relation to individual prognostic factors (stage of disease, depth of myometrial invasion, tumor grade, risk type of disease). RESULTS: In the case of HE4, we demonstrated a statistically significant difference (P < 0.001) between patients with low and high risk of the disease. In our model, achieving the maximum sum of sensitivity and specificity, HE4 shows a sensitivity of 72.4% and a specificity of 75.4% for the cut-off 76.5 pmol/L and is a better predictor in distinguishing the high-risk patients than CA125 (area under the curve 0.77 for HE vs 0.71 for CA125). CONCLUSION: HE4 is a marker that could complement the findings of imaging techniques and that may be useful in decision-making on how to individualize surgical staging. The possibility of its introduction as an independent marker in routine practice remains, at the moment however, limited. The optimal cut-off for HE4 has not been established yet and further studies are needed.

• Klíčová slova
• endometrial cancer, human epididymis protein 4, risk status of disease, surgical staging,
• MeSH
• antigen CA-125 krev   MeSH
• endometroidní karcinom krev   patologie   MeSH
• lidé MeSH
• membránové proteiny krev   MeSH
• myometrium patologie   MeSH
• nádorové biomarkery krev   MeSH
• nádory endometria krev   patologie   MeSH
• protein WFDC2 MeSH
• proteiny metabolismus   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein WFDC2 MeSH
• proteiny MeSH
• WFDC2 protein, human MeSH Prohlížeč

BACKGROUND: The occurrence of catamenial pneumothorax (CP) is rare, and the awareness of this diagnosis among physicians is insufficient. CP is highly correlated with pelvic endometriosis and remains the most common form of thoracic endometriosis syndrome. Circulating endometrial cells (CECs) have been previously detected in patients with pelvic endometriosis. Could CECs bring new insights into pneumothorax management? METHODS: This study aims to describe the occurrence and molecular characteristics of CECs in women with spontaneous pneumothorax (SP) (N = 20) with high suspicion of its catamenial character. CECs were enriched from peripheral blood by size-based separation (MetaCell). In addition to cytomorphology, gene expression profiling of captured cells was performed for 24 endometriosis-associated genes. RESULTS: CECs were present in all 20 patients with SP. Enriched CECs exhibited four character features: epithelial, stem cell-like, stroma-like, and glandular. However, not all of them were present in every sampling. Gene expression profiling revealed two distinct phenotypes of CECs in SP and/or CP: one of them refers to the diaphragm openings syndrome and the other to endometrial tissue pleural implantations. Comparisons of the gene expression profiles of CECs in pneumothorax (CECs-SP group) with CECs in pelvic endometriosis (CECs-non-SP group) have revealed significantly higher expression of HER2 in the CECs-SP group compared with the CECs-non-SP group. CONCLUSIONS: This proof-of-concept study demonstrates successful isolation and characterization of CECs in patients with SP. Identification of CECs in SP could alert endometriosis involvement and help early referral to gynecologic consultation for further examination and treatment.

• Klíčová slova
• MetaCell, biomarker, catamenial pneumothorax, circulating endometrial cells, culturing, endometriosis, gene expression profiling, in vitro, liquid biopsy,
• MeSH
• antigen CA-125 genetika   MeSH
• dospělí MeSH
• endometrióza krev   genetika   MeSH
• endometrium cytologie   MeSH
• keratin-18 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mladý dospělý MeSH
• mucin 1 genetika   MeSH
• nemoci pleury krev   genetika   MeSH
• pneumotorax krev   diagnóza   genetika   MeSH
• receptor erbB-2 genetika   MeSH
• studie případů a kontrol MeSH
• tekutá biopsie MeSH
• transkriptom MeSH
• vimentin genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CA-125 MeSH
• ERBB2 protein, human MeSH Prohlížeč
• keratin-18 MeSH
• KRT18 protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• MUC1 protein, human MeSH Prohlížeč
• MUC16 protein, human MeSH Prohlížeč
• mucin 1 MeSH
• receptor erbB-2 MeSH
• VIM protein, human MeSH Prohlížeč
• vimentin MeSH

AIM: To develop and validate a biomarker-based index to optimize referral and diagnosis of patients with suspected ovarian cancer. Furthermore, to compare this new index with the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS: A training study, consisting of patients with benign ovarian disease (n=809) and ovarian cancer (n=246), was used to develop the Copenhagen Index (CPH-I) utilizing the variables serum HE4, serum CA125 and patient age. Eight international studies provided the validation population; comprising 1060 patients with benign ovarian masses and 550 patients with ovarian cancer. RESULTS: Overall, 2665 patients were included. CPH-I was highly significant in discriminating benign from malignant ovarian disease. At the defined cut-off of 0.070 for CPH-I the sensitivity and specificity were 95.0% and 78.4% respectively in the training cohort and 82.0% and 88.4% in the validation cohort. Comparison of CPH-I, ROMA and RMI demonstrated area-under-curve (AUC) at 0.960, 0.954 and 0.959 respectively in the training study and 0.951, 0.953 and 0.935 respectively in the validation study. Using a sensitivity of 95.0%, the specificities for CPH-I, ROMA and RMI in the training cohort were 78.4%, 71.7% and 81.5% respectively, and in the validation cohort 67.3%, 70.7% and 69.5% respectively. CONCLUSION: All three indices perform well at the clinically relevant sensitivity of 95%, but CPH-I, unlike RMI and ROMA, is independent of ultrasound and menopausal status, and may provide a simple index to optimize referral of women with suspected ovarian cancer.

• Klíčová slova
• Age, Biomarkers, CA125, CPH-I, Copenhagen Index, HE4, Ovarian cancer, Tumor markers,
• MeSH
• algoritmy MeSH
• antigen CA-125 krev   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny krev   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multivariační analýza MeSH
• nádorové biomarkery krev   MeSH
• nádory vaječníků krev   diagnóza   patologie   MeSH
• nemoci ovaria krev   diagnóza   patologie   MeSH
• prospektivní studie MeSH
• protein WFDC2 MeSH
• proteiny metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statistické modely MeSH
• stupeň závažnosti nemoci MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein WFDC2 MeSH
• proteiny MeSH
• WFDC2 protein, human MeSH Prohlížeč

The main focus of the study was to detect circulating tumor cells (CTCs) in ovarian cancer (OC) patients using a new methodological approach (MetaCell(TM)) which is based on size-dependent separation of CTCs and subsequent cytomorphological evaluation. Cytomorphological evaluation using vital fluorescence microscopy approach enables to use the captured cells for further RNA/DNA analysis. The cytomorphological analysis is then completed by gene expression analysis (GEA). GEA showed that relative expression of EPCAM is elevated in CTC-enriched fractions in comparison to the whole peripheral blood sample and that the expression grows with in vitro cultivation time. Comparison of the relative gene expression level in the group of peripheral blood samples and CTC-fraction samples confirmed a statistically significant difference for the following genes (p < 0.02): KRT7, WT1, EPCAM, MUC16, MUC1, KRT18 and KRT19. Thus, we suggest that the combination of the above listed genes could confirm CTCs presence in OC patients with higher specificity than when GEA tests are performed for one marker only. The GEA revealed two separate clusters identifying patients with or without CTCs.

• Klíčová slova
• CTCs, MetaCell, circulating tumor cells, cultivation, gene expression, in vitro, ovarian cancer,
• Publikační typ
• časopisecké články MeSH

Women with ovarian cancer often present at advanced stage of disease. The outcome depends mainly on the stage of disease at first diagnosis, but also on the quality of treatment. For individualised tumour treatment, detailed assessment of tumour extension using modern imaging is crucial. Ultrasound remains the initial and most important imaging method for ovarian cancer detection. Although increasing evidence shows that ultrasound is an accurate technique to stage and follow up ovarian cancer, it requires an experienced examiner capable of examining both the pelvis and the abdomen. Computed tomography is the most commonly used imaging modality for preoperative staging and follow up. Magnetic resonance imaging remains a second-line imaging method for solving problems, mainly in the pelvis. Positron emission tomography combined with computed tomography is the optimal imaging technique for suspected recurrence, particularly in women with rising CA 125 levels, but negative results of conventional imaging methods.

• Klíčová slova
• CT, FIGO staging, MRI, PET/CT, follow up, ovarian cancer staging, ultrasound,
• MeSH
• adjuvantní chemoterapie MeSH
• antigen CA-125 analýza   MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• magnetická rezonanční tomografie MeSH
• membránové proteiny analýza   MeSH
• multidetektorová počítačová tomografie MeSH
• nádory vaječníků diagnóza   diagnostické zobrazování   farmakoterapie   patologie   chirurgie   MeSH
• počítačová rentgenová tomografie MeSH
• pozitronová emisní tomografie MeSH
• staging nádorů MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč

The focus of the study was to implement a new workflow for circulating tumor cells (CTCs) characterization that would allow the analysis of CTCs on a cytomorphological and molecular level in patients with diagnosed gynecological cancer. Our findings may be useful in future cancer patient management. The study introduces a size-based enrichment (MetaCell(®)) method for the separation of viable CTCs, followed by CTCs culturing in vitro and gene expression characterization. It is based on the observation of CTCs and DTCs (Disseminated Tumor Cells) in several case studies of ovarian, endometrial and cervical cancer by means of cytomorphology and gene expression profiling. The viability of the enriched CTCs was estimated using vital and lethal fluorescence nuclear staining. This type of staining may be predictive for the success rate of subsequent CTC growth in vitro. To identify CTCs in the enriched CTC fraction, cytomorphological evaluations based on vital fluorescence staining were followed by gene expression analysis of tumor-associated (TA) genes. Cytokeratin expression (KRT7, KRT19) was analyzed in combination with MUC1, MUC16, CD24, CD44 and ALDH1. Gene expression analysis has shown that short-term in vitro culture enhanced the differentiation process of the captured CTCs growing on a membrane. On the other hand, redundant white blood cells captured on the membrane were eliminated during a short-term culture. The most frequently elevated genes in ovarian cancer (serous type) are EPCAM, KRT19 and MUC1. It has been demonstrated that CTC presence revealed by cytomorphological evaluation may be usefully complemented by TA-gene expression analysis, to increase the sensitivity of the analysis.

• Klíčová slova
• CTCs, cervical cancer, cultivation, endometrial cancer, gynecological cancers, in vitro, ovarian cancer,
• Publikační typ
• časopisecké články MeSH