-
Je něco špatně v tomto záznamu ?
Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance
P. Dundr, N. Hájková, M. Kendall Bártů, D. Cibula, J. Drozenová, P. Fabian, O. Fadare, F. Frühauf, J. Hausnerová, J. Hojný, J. Laco, SF. Lax, R. Matěj, G. Méhes, R. Michálková, K. Němejcová, N. Singh, S. Stolnicu, M. Švajdler, T. Zima, WG....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
- MeSH
- imunohistochemie MeSH
- lidé MeSH
- mucinózní adenokarcinom * diagnóza genetika MeSH
- mutace MeSH
- nádorový supresorový protein p53 genetika metabolismus MeSH
- nádory vaječníků * diagnóza genetika metabolismus MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
Department of Oncological Pathology Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Pathology Belfast Health and Social Care Trust Belfast UK
Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary
Department of Pathology General Hospital Graz 2 Graz Austria
Department of Pathology University of California San Diego San Diego CA USA
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc23016116
- 003
- CZ-PrNML
- 005
- 20231026110405.0
- 007
- ta
- 008
- 231013s2023 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.pathol.2023.04.008 $2 doi
- 035 __
- $a (PubMed)37500307
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Dundr, Pavel $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. Electronic address: pavel.dundr@vfn.cz
- 245 10
- $a Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance / $c P. Dundr, N. Hájková, M. Kendall Bártů, D. Cibula, J. Drozenová, P. Fabian, O. Fadare, F. Frühauf, J. Hausnerová, J. Hojný, J. Laco, SF. Lax, R. Matěj, G. Méhes, R. Michálková, K. Němejcová, N. Singh, S. Stolnicu, M. Švajdler, T. Zima, WG. McCluggage, I. Stružinská
- 520 9_
- $a 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.
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a nádorový supresorový protein p53 $x genetika $x metabolismus $7 D016159
- 650 _2
- $a imunohistochemie $7 D007150
- 650 12
- $a nádory vaječníků $x diagnóza $x genetika $x metabolismus $7 D010051
- 650 _2
- $a prognóza $7 D011379
- 650 _2
- $a mutace $7 D009154
- 650 12
- $a mucinózní adenokarcinom $x diagnóza $x genetika $7 D002288
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Hájková, Nikola $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Kendall Bártů, Michaela $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Cibula, David $u Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Drozenová, Jana $u Department of Pathology, Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- 700 1_
- $a Fabian, Pavel $u Department of Oncological Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
- 700 1_
- $a Fadare, Oluwole $u Department of Pathology, University of California San Diego, San Diego, CA, USA
- 700 1_
- $a Frühauf, Filip $u Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Hausnerová, Jitka $u Department of Pathology, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Hojný, Jan $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Laco, Jan $u The Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
- 700 1_
- $a Lax, Sigurd F $u Department of Pathology, General Hospital Graz II, Graz, Austria; Johannes Kepler University Linz, Austria
- 700 1_
- $a Matěj, Radoslav $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; Department of Pathology, Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic; Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University, Thomayer University Hospital, Prague, Czech Republic
- 700 1_
- $a Méhes, Gábor $u Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- 700 1_
- $a Michálková, Romana $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Němejcová, Kristýna $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Singh, Naveena $u Department of Cellular Pathology, Barts Health NHS Trust, Blizard Institute of Core Pathology, Queen Mary University of London, London, UK
- 700 1_
- $a Stolnicu, Simona $u Department of Pathology, George E. Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, Romania
- 700 1_
- $a Švajdler, Marián $u Šikl's Department of Pathology, The Faculty of Medicine and Faculty Hospital in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Zima, Tomáš $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a McCluggage, W Glenn $u Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK
- 700 1_
- $a Stružinská, Ivana $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 773 0_
- $w MED00003708 $t Pathology $x 1465-3931 $g Roč. 55, č. 6 (2023), s. 785-791
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/37500307 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20231013 $b ABA008
- 991 __
- $a 20231026110358 $b ABA008
- 999 __
- $a ok $b bmc $g 1999937 $s 1202478
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 55 $c 6 $d 785-791 $e 20230711 $i 1465-3931 $m Pathology $n Pathology $x MED00003708
- LZP __
- $a Pubmed-20231013
