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001-es BibID:BIBFORM112820
035-os BibID:(scopus)85129859908 (wos)000795504200001
Első szerző:Dundr, Pavel
Cím:The cytokeratin 17 expression in primary ovarian tumors has diagnostic but not prognostic significance / Dundr Pavel, Bazalová Barbora, Bártu Michaela, Bosse Tjalling, Drozenová Jana, Fabian Pavel, Fadare Oluwole, Hausnerová Jitka, Jaksa Radek, Laco Jan, Lax Sigurd F., Matej Radoslav, McCluggage W. Glenn, Méhes Gábor, Michálková Romana, Nemejcová Kristyna, Singh Naveena, Stolnicu Simona, Skapa Petr, Svajdler Marián, Struzinská Ivana
Dátum:2022
ISSN:0945-6317
Megjegyzések:We assessed the value of cytokeratin 17 (CK17) expression for the differential diagnosis between primary ovarian mucinous tumors and metastases from the gastrointestinal tract (GIT) and the significance of CK17 expression in a broad spectrum of primary ovarian tumors with respect to their prognosis. The sample set consisted of 554 primary ovarian tumors and 255 GIT tumors. In the primary ovarian tumors, a higher CK17 expression (in > 10% of tumors cells) was present only in 0?11.4% of all tumors (including mucinous tumors, micropapillary serous borderline tumors, clear cell, endometrioid, and high-grade serous carcinomas). The only exception was low-grade serous carcinoma, where higher CK17 expression was present in 24% of cases. Concerning GIT tumors, the higher levels of CK 17 expression (in > 10% of tumor cells) were observed in the upper GIT tumors (68.5% of pancreatic ductal adenocarcinoma, 61.6% of gallbladder adenocarcinoma, and 46% of gastric adenocarcinoma), which differs substantially not only from most of the primary ovarian tumors, but also from colorectal carcinoma (3.7%; p < 0.001). The results of our study suggest that expression of CK17 can potentially be used as an adjunct marker in differential diagnosis between primary ovarian mucinous tumors and metastases from the upper GIT, but not from colorectal carcinoma. However, in GIT tumors, CK17 can be used in the differential diagnosis between adenocarcinomas of the upper and lower GIT. Statistical analysis did not reveal strong association of CK17 expression with clinicopathological variables or patient outcomes in any primary ovarian tumors.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Virchows Archiv. - 481 : 2 (2022), p. 201-212. -
További szerzők:Bazalová, Barbora Bártủ, Michaela Bosse, Tjalling Drozenová, Jana Fabian, Pavel Fadare, Oluwole Hausnerová, Jitka Jaksa, Radek Laco, Jan Lax, Sigurd F. Matej, Radoslav McCluggage, W. Glenn Méhes Gábor (1966-) (patológus) Michálková, Romana Nĕmejcová, Kristýna Singh, Naveena Stolnicu, Simona Škapa, Petr Svajdler, Marián Struzinská, Ivana
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2.

001-es BibID:BIBFORM106881
035-os BibID:(cikkazonosító)100040 (Scopus)85148085127 (WoS)000982550100001
Első szerző:Dundr, Pavel
Cím:Primary Mucinous Tumors of the Ovary : An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories / Dundr Pavel, Bártu Michaela, Bosse Tjalling, Bui Quang Hiep, Cibula David, Drozenová Jana, Fabian Pavel, Fadare Oluwole, Hausnerová Jitka, Hojny Jan, Hájková Nikola, Jaksa Radek, Laco Jan, Lax Sigurd F., Matej Radoslav, Méhes Gábor, Michálková Romana, Safanda Adam, Nemejcová Kristyna, Singh Naveena, Stolnicu Simona, Svajdler Marián, Zima Tomás, Struzinská Ivana, McCluggage W. Glenn
Dátum:2023
ISSN:0893-3952
Megjegyzések:Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (k= 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Modern Pathology. - 36 : 1 (2023), p. 1-14. -
További szerzők:Bártủ, Michaela Bosse, Tjalling Bui, Quang Hiep Cibula, David Drozenová, Jana Fabian, Pavel Fadare, Oluwole Hausnerová, Jitka Hojny, Jan Hájková, Nikola Jaksa, Radek Laco, Jan Lax, Sigurd F. Matej, Radoslav Méhes Gábor (1966-) (patológus) Michálková, Romana Safanda, Adam Nĕmejcová, Kristýna Singh, Naveena Stolnicu, Simona Svajdler, Marián Zima Tomás Struzinská, Ivana McCluggage, W. Glenn
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM116552
035-os BibID:(scopus)85163358484 (wos)001067763800001
Első szerző:Hájková, Nikola
Cím:Microsatellite instability in non-endometrioid ovarian epithelial tumors : a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes / Hájková Nikola, Bártu Michaela Kendall, Cibula David, Drozenová Jana, Fabian Pavel, Fadare Oluwole, Frühauf Filip, Hausnerová Jitka, Hojny Jan, Krkavcová Eva, Laco Jan, Lax Sigurd F., Matej Radoslav, Méhes Gábor, Michálková Romana, Nemejcová Kristyna, Singh Naveena, Stolnicu Simona, Svajdler Marián, Zima Tomás, McCluggage Wilson Glenn, Struzinská Ivana, Dundr Pavel
Dátum:2023
ISSN:1931-5244
Megjegyzések:Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method. Except for high-grade serous carcinoma, we correlated the findings of IHC and PCR with NGS-based MSI testing. We compared the results with somatic and germline mutation in MMR genes. Among the whole cohort, seven MMR-D cases, all clear cell carcinomas (CCC), were found. On PCR analysis, 6 cases were MSI-high and one was MSS. In all cases, mutation of an MMR gene was found; in 2 cases, the mutation was germline (Lynch syndrome). An additional 5 cases with a mutation in MMR gene(s) with MSS status and without MMR-D were identified. We further utilized sequence capture NGS for MSI testing. Employing 53 microsatellite loci provided high sensitivity and specificity. Our study shows that MSI occurs in 7% of CCC while it is rare or absent in other nonendometrioid ovarian neoplasms. Lynch syndrome was present in 2% of patients with CCC. However, some cases with MSH6 mutation can evade all testing methods, including IHC, PCR, and NGS-MSI.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Colorectal Neoplasms,Hereditary Nonpolyposis
DNA Mismatch Repair
Female
High-Throughput Nucleotide Sequencing
Humans
Microsatellite Instability
Mutation
Neoplasms, Glandular and Epithelial
Polymerase Chain Reaction
Turcot syndrome
DNA mismatch repair protein MSH2
mismatch repair protein
mismatch repair protein PMS2
MutL protein homolog 1
protein MSH6
adult
aged
Article
cancer grading
clear cell carcinoma
colloid carcinoma
controlled study
epithelium tumor
female
germline mutation
high throughput sequencing
histopathology
human
human cell
human tissue
interrater reliability
major clinical study
microsatellite instability
microsatellite marker
ovary tumor
polymerase chain reaction
protein expression
somatic mutation
tumor growth
World Health Organization
genetics
glandular and epithelial neoplasms
hereditary nonpolyposis colorectal cancer
Immunohistochemistry
Megjelenés:Translational Research. - 260 (2023), p. 61-68. -
További szerzők:Bártủ, Michaela Cibula, David Drozenová, Jana Fabian, Pavel Fadare, Oluwole Frühauf, Filip Hausnerová, Jitka Hojná, Jan Krkavcová, Eva Laco, Jan Lax, Sigurd F. Matej, Radoslav Méhes Gábor (1966-) (patológus) Michálková, Romana Nĕmejcová, Kristýna Singh, Naveena Stolnicu, Simona Svajdler, Marián Zima Tomás McCluggage, W. Glenn Struzinská, Ivana Dundr, Pavel
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM076543
Első szerző:Hájková, Nikola
Cím:Synchronous endometrioid endometrial and ovarian carcinomas are biologically related : a clinico-pathological and molecular (next generation sequencing) study of 22 cases / Hájková Nikola, Tichá Ivana, Hojná Jan, Nĕmejcová Kristýna, Bártủ Michaela, Michálková Romana, Zikán Michal, Cibula David, Laco Jan, Geryk Tomáŝ, Méhes Gábor, Dundr Pavel
Dátum:2018
ISSN:1792-1074 1792-1082
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Oncology Letters. - 17 (2018), p. 2207-2214. -
További szerzők:Tichá, Ivana Hojná, Jan Nĕmejcová, Kristýna Bártủ, Michaela Michálková, Romana Zikán, Michal Cibula, David Laco, Jan Geryk, Tomáŝ Méhes Gábor (1966-) (patológus) Dundr, Pavel
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Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM112827
035-os BibID:(scopus)85149153484 (wos)000941171800001
Első szerző:Nĕmejcová, Kristýna
Cím:A comprehensive immunohistochemical analysis of 26 markers in 250 cases of serous ovarian tumors / Nemejcová Kristyna, Safanda Adam, Bártu Michaela Kendall, Michálková Romana, Drozenová Jana, Fabian Pavel, Hausnerová Jitka, Laco Jan, Matej Radoslav, Méhes Gábor, Skapa Petr, Struzinská Ivana, Dundr Pavel
Dátum:2023
ISSN:1746-1596
Megjegyzések:Background: We examined a large cohort of serous tubo-ovarian tumors with 26 immunohistochemical markers, with the aim to assess their value for differential diagnosis and prognosis. Methods: Immunohistochemical analyses with 26 immunomarkers were performed on 250 primary tubo-ovarian tumors including 114 high grade serous carcinomas (HGSC), 97 low grade serous carcinomas (LGSC), and 39 serous borderline tumors (micropapillary variant, mSBT). The associations of overall positivity with clinicopathological charac- teristics were evaluated using the chi-squared test or Fisher's Exact test. Results: We found significantly different expression of p53, p16, ER, PR, PTEN, PAX2, Mammaglobin, RB1, Cyclin E1, stathmin, LMP2, L1CAM, CD44, and Ki67 in HGSCs compared to LGSCs. No significant differences were found between LGSC and mSBT. None of the other included markers (PAX8, ARID1A, HNF1B, Napsin A, CDX2, SATB2, MUC4, BRG1, AMACR, TTF1, BCOR, NTRK) showed any differences between the investigated serous tumors. Regarding the prognosis, only PR and stathmin showed a statistically significant prognostic meaning in LGSCs, with better overall survival (OS) and recurrence-free survival (RFS) in cases positive for PR, and worse outcome (RFS) for stathmin. None of the study markers showed prognostic significance in HGSCs. Conclusion: We provided an extensive immunohistochemical analysis of serous ovarian/tubo-ovarian tumors. Although we found some differences in the expression of some markers in HGSCs compared to LGSCs, only p53, p16, and Ki67 seem to be useful in real diagnostic practice. We also suggested the best discriminative cut-off for Ki67 (10% of positive tumor cells) for distinguishing HGSC from LGSC. We found prognostic significance of PR and stathmin in LGSCs. Moreover, the high expression of stathmin could also be of predictive value in ovarian carcinomas as target specific anti-stathmin effectors are potential therapeutic targets.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Diagnostic Pathology. - 18 : 1 (2023), p. 1-12. -
További szerzők:Safanda, Adam Bártủ, Michaela Michálková, Romana Drozenová, Jana Fabian, Pavel Hausnerová, Jitka Laco, Jan Matej, Radoslav Méhes Gábor (1966-) (patológus) Škapa, Petr Struzinská, Ivana Dundr, Pavel
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Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM112826
035-os BibID:(cikkazonosító)15 (scopus)85147393025 (wos)000926120000002
Első szerző:Nĕmejcová, Kristýna
Cím:A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors / Nemejcová Kristyna, Bártu Michaela Kendall, Michálková Romana, Drozenová Jana, Fabian Pavel, Fadare Oluwole, Hausnerová Jitka, Laco Jan, Matej Radoslav, Méhes Gábor, Singh Naveena, Stolnicu Simona, Skapa Petr, Svajdler Marián, Struzinská Ivana, Cibula David, Kocian Roman, Lax Sigurd F., McCluggage W. Glenn, Dundr Pavel
Dátum:2023
ISSN:1746-1596
Megjegyzések:Background: IMP2 and IMP3 are mRNA binding proteins involved in carcinogenesis. We examined a large cohort of ovarian tumors with the aim to assess the value of IMP2 and IMP3 for differential diagnosis, and to assess their prognostic significance. Methods: Immunohistochemical analyses with antibodies against IMP2 and IMP3 were performed on 554 primary ovarian tumors including 114 high grade serous carcinomas, 100 low grade serous carcinomas, 124 clear cell carcinomas, 54 endometrioid carcinomas, 34 mucinous carcinomas, 75 mucinous borderline tumors, and 41 serous border- line tumors (micropapillary variant). The associations of overall positivity with clinicopathological characteristics were evaluated using the chi-squared test or Fisher's Exact test. Results: We found IMP2 expression (in more than 5% of tumor cells) in nearly all cases of all tumor types, so the prognostic meaning could not be analyzed. The positive IMP3 expression (in more than 5% of tumor cells) was most common in mucinous carcinomas (82%) and mucinous borderline tumors (81%), followed by high grade serous (67%) and clear cell carcinomas (67%). The expression was less frequent in endometrioid carcinomas (39%), low grade serous carcinomas (23%), and micropapillary variant of serous borderline tumors (20%). Prognostic significance of IMP3 could be evaluated only in low grade serous carcinomas in the case of relapse-free survival, where negative cases showed better RFS (p = 0.033). Conclusion: Concerning differential diagnosis our results imply that despite the differences in expression in the different ovarian tumor types, the practical value for diagnostic purposes is limited. Contrary to other solid tumors, we did not find prognostic significance of IMP3 in ovarian cancer, with the exception of RFS in low grade serous carcinomas. However, the high expression of IMP2 and IMP3 could be of predictive value in ovarian carcinomas since IMP proteins are potential therapeutical targets.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Diagnostic Pathology. - 18 : 1 (2023), p. 1-10. -
További szerzők:Bártủ, Michaela Michálková, Romana Drozenová, Jana Fabian, Pavel Fadare, Oluwole Hausnerová, Jitka Laco, Jan Matej, Radoslav Méhes Gábor (1966-) (patológus) Singh, Naveena Stolnicu, Simona Škapa, Petr Svajdler, Marián Struzinská, Ivana Cibula, David Kocian, Roman Lax, Sigurd F. McCluggage, W. Glenn Dundr, Pavel
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Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM113119
035-os BibID:(wos)001002555100001 (scopus)85161669317 (cikkazonosító)72
Első szerző:Struzinská, Ivana
Cím:A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations / Struzinská Ivana, Hájková Nikola, Hojny Jan, Krkavcová Eva, Michálková Romana, Dvorák Jirí, Nemejcová Kristyna, Matej Radoslav, Laco Jan, Drozenová Jana, Fabian Pavel, Hausnerová Jitka, Méhes Gábor, Skapa Petr, Svajdler Marián, Cibula David, Frühauf Filip, Bártu Michaela Kendall, Dundr Pavel
Dátum:2023
ISSN:1746-1596
Megjegyzések:Background Molecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking. Methods 113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance. Results The most frequent mutations were detected in genes ARID1A, PIK3CA, TERTp, KRAS, TP53, ATM, PPP2R1A, NF1, PTEN, and POLE (51,47,27,18,13,10,7,6,6, and 4%, respectively). TMB-High cases were detected in 9% of cases. Cases with POLEmut and/or MSI-High had better relapse-free survival. RNA-Seq revealed gene fusions in 14/105 (13%) cases, and heterogeneous expression pattern. The majority of gene fusions affected tyrosine kinase receptors (6/14; four of those were MET fusions) or DNA repair genes (2/14). Based on the mRNA expression pattern, a cluster of 12 OCCCs characterized by overexpression of tyrosine kinase receptors (TKRs) AKT3, CTNNB1, DDR2, JAK2, KIT, or PDGFRA (p < 0.00001) was identified. Conclusions The current work has elucidated the complex genomic and transcriptomic molecular hallmarks of primary OCCCs. Our results confirmed the favorable outcomes of POLEmut and MSI-High OCCC. Moreover, the molecular landscape of OCCC revealed several potential therapeutical targets. Molecular testing can provide the potential for targeted therapy in patients with recurrent or metastatic tumors.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Diagnostic Pathology. - 18 : 1 (2023), p. 1-12. -
További szerzők:Hájková, Nikola Hojny, Jan Krkavcová, Eva Michálková, Romana Dvorak, Jiri Nĕmejcová, Kristýna Matej, Radoslav Laco, Jan Drozenová, Jana Fabian, Pavel Hausnerová, Jitka Méhes Gábor (1966-) (patológus) Škapa, Petr Svajdler, Marián Cibula, David Frühauf, Filip Bártủ, Michaela Dundr, Pavel
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