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1.

001-es BibID:BIBFORM116546
035-os BibID:(scopus)85165673383 (wos)001082559400001
Első szerző:Dundr, Pavel
Cím:Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance / Dundr Pavel, Hájková Nikola, Kendall Bártu Michaela, Cibula David, Drozenová Jana, Fabian Pavel, Fadare Oluwole, Frühauf Filip, Hausnerová Jitka, Hojny Jan, Laco Jan, Lax Sigurd F., Matej Radoslav, Méhes Gábor, Michálková Romana, Nemejcová Kristyna, Singh Naveena, Stolnicu Simona, Svajdler Marián, Zima Tomás, McCluggage W. Glenn, Struzinská Ivana
Dátum:2023
ISSN:0031-3025
Megjegyzések:In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aberrant staining in ovarian carcinoma [overexpression (♭all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tumours (strong nuclear p53 staining in ?12 consecutive tumour cells) and correlated the results with next generation sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mutation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53 wild-type on sequencing. Three cases had normal p53 expression but contained a TP53 mutation. Overall, IHC predicted the TP53 mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predictive value of 92.7%. When comparing MC cases with wild-type TP53 versus those with TP53 mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in ?12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53 mutation but the TP53 mutation status has no prognostic significance in either MC or MBT.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Mucinous tumours
ovary
p53
TP53
immunohistochemistry
next generation sequencing
Megjelenés:Pathology. - 55 : 6 (2023), p. 785-791. -
További szerzők:Hájková, Nikola Kendall Bártů, Michaela Cibula, David Drozenová, Jana Fabian, Pavel Fadare, Oluwole Frühauf, Filip Hausnerová, Jitka Hojná, Jan 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
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

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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Intézményi repozitóriumban (DEA) tárolt változat
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3.

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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4.

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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5.

001-es BibID:BIBFORM116529
035-os BibID:(scopus)85169932064 (wos)001060259500001
Első szerző:Kendall Bártů, Michaela
Cím:HER2 status as a potential predictive biomarker for ovarian clear cell carcinoma / Kendall Bártu Michaela, Nemejcová Kristyna, Michálková Romana, Struzinská Ivana, Hájková Nikola, Hojny Jan, Krkavcová Eva, Laco Jan, Matej Radoslav, Drozenová Jana, Méhes Gábor, Fabian Pavel, Hausnerová Jitka, Svajdler Marián, Skapa Petr, Cibula David, Zima Tomás, Dundr Pavel
Dátum:2023
ISSN:0945-6317
Megjegyzések:Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2). Our main objective was to characterize the HER2 status using immunohistochemistry (IHC) and FISH on 118 OCCCs, also considering the novel paradigm of HER2-zero and HER2-low status. Other aims included determination of the association between HER2 status and survival, HER2 gene DNA and RNA NGS analysis, HER2 gene expression analysis, and correlation between IHC and gene expression in HER2-zero and HER2-low cases. Cases with HER2 overexpression/amplification accounted for 5.1% (6/118), with additional 3% harbouring HER2 gene mutation. The remaining 112 (94.9%) cases were HER2-negative. Of these, 75% were classified as HER2-zero and 25% as HER2-low. This percentage of HER2 aberrations is significant concerning their possible therapeutic influence. Cases from the HER2-zero group showed significantly better survival. Although this relationship lost statistical significance in multivariate analysis, the results have potential therapeutic significance. HER2 gene expression analysis showed a significant correlation with HER2 IHC status in the entire cohort (HER2-positive vs. HER2-negative), while in the cohort of only HER2-negative cases, the results did not reach statistical significance, suggesting that gene expression analysis would not be suitable to confirm the subdivision into HER2-low and HER2-zero. Our results also emphasize the need for standardized HER2 testing in OCCC to determine the best predictor of clinical response.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
HER2
Ovarian clear cell carcinoma
Immunohistochemistry
Gynecopathology
Ovarian cancer
Megjelenés:Virchows Archiv. - 483 : 4 (2023), p. 497-507. -
További szerzők:Nĕmejcová, Kristýna Michálková, Romana Struzinská, Ivana Hájková, Nikola Hojny, Jan Krkavcová, Eva Laco, Jan Matej, Radoslav Drozenová, Jana Méhes Gábor (1966-) (patológus) Fabian, Pavel Hausnerová, Jitka Svajdler, Marián Škapa, Petr Cibula, David Zima Tomás Dundr, Pavel
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Intézményi repozitóriumban (DEA) tárolt változat
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6.

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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7.

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
Borító:

8.

001-es BibID:BIBFORM116533
035-os BibID:(scopus)85168619897 (wos)001063398000003
Első szerző:Safanda, Adam
Cím:Immunohistochemical expression of PRAME in 485 cases of epithelial tubo-ovarian tumors / Safanda Adam, Kendall Bártu Michaela, Michálková Romana, Struzinská Ivana, Drozenová Jana, Fabián Pavel, Hausnerová Jitka, Laco Jan, Matej Radoslav, Skapa Petr, Svajdler Marián, Spurková Zuzana, Méhes Gábor, Dundr Pavel, Nemejcová Kristyna
Dátum:2023
ISSN:0945-6317
Megjegyzések:Preferentially expressed antigen of melanoma (PRAME) is a cancer/testis antigen selectively expressed in somatic tissues and various solid malignant tumors and is associated with poor prognostic outcome. Our research aimed to comprehensively compare its expression in a large cohort of tubo-ovarian epithelial tumors and examine its correlation with our clinico-pathologic data, as well as to assess its potential use in diagnostics and therapy. We examined 485 cases of epithelial tubo-ovarian tumors including 107 clear cell carcinomas (CCC), 52 endometroid carcinomas (EC), 103 high grade serous carcinomas (HGSC), 119 low grade serous carcinomas (LGSC)/micropapillary variant of serous borderline tumors (mSBT), and 104 cases of mucinous carcinomas (MC)/mucinous borderline tumors (MBT). The immunohistochemical analysis was performed using TMAs. The highest levels of expression were seen in EC (60%), HGSC (62%), and CCC (56%), while expression in LGSC/mSBT (4%) and MC/MBT (2%) was rare. The clinico-pathologic correlations and survival analysis showed no prognostic significance. The results of our study showed that PRAME is neither prognostic nor a suitable ancillary marker in the differential diagnosis of tubo-ovarian epithelial tumors. Nevertheless, knowledge about the PRAME expression may be important concerning its potential predictive significance, because targeting PRAME as a potential therapeutic option is currently under investigation.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Cancer
Immunohistochemistry
Ovarian tumors
PRAME
Megjelenés:Virchows Archiv. - 483 : 4 (2023), p. 509-516. -
További szerzők:Kendall Bártů, Michaela Michálková, Romana Struzinská, Ivana Drozenová, Jana Fabian, Pavel Hausnerová, Jitka Laco, Jan Matej, Radoslav Škapa, Petr Svajdler, Marián Špůrková, Zuzana Méhes Gábor (1966-) (patológus) Dundr, Pavel Nĕmejcová, Kristýna
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

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
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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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