Refined criteria for p53 expression in ovarian mucinous tumours
are highly concordant with TP53 mutation status, but p53
expression/TP53 status lack prognostic significance

J 2023

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, Nikola HAJKOVA, Michaela BARTU KENDALL, David CIBULA, Jana DROZENOVA et. al.

Základní údaje

Originální název

Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance

Autoři

DUNDR, Pavel (203 Česká republika, garant), Nikola HAJKOVA (203 Česká republika), Michaela BARTU KENDALL (203 Česká republika), David CIBULA (203 Česká republika), Jana DROZENOVA (203 Česká republika), Pavel FABIAN (203 Česká republika), Oluwole FADARE, Filip FRUHAUF (203 Česká republika), Jitka HAUSNEROVÁ (203 Česká republika, domácí), Jan HOJNY (203 Česká republika), Jan LACO (203 Česká republika), Sigurd F LAX, Radoslav MATEJ (203 Česká republika), Gabor MEHES, Romana MICHALKOVA (203 Česká republika), Kristyna NEMEJCOVA (203 Česká republika), Naveena SINGH, Simona STOLNICU (203 Česká republika), Marian SVAJDLER (203 Česká republika), Tomas ZIMAS (203 Česká republika), W Glenn MCCLUGGAGE a Vana STRUZINSKA (203 Česká republika)

Vydání

PATHOLOGY, AMSTERDAM, ELSEVIER, 2023, 0031-3025

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30109 Pathology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.500 v roce 2022

Kód RIV

RIV/00216224:14110/23:00132980

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/j.pathol.2023.04.008

UT WoS

001082559400001

Klíčová slova anglicky

Mucinous tumours; ovary; p53; TP53; immunohistochemistry; next generation sequencing

Štítky

14110230, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 1. 2024 13:35, Mgr. Tereza Miškechová

Anotace

V originále

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 aber-rant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tu-mours (strong nuclear p53 staining in >12 consecutive tumour cells) and correlated the results with next genera-tion 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 mu-tation 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 predic-tive 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.

Návaznosti

90233, velká výzkumná infrastruktura

Název: BBMRI.cz IV

Citovat

DUNDR, Pavel, Nikola HAJKOVA, Michaela BARTU KENDALL, David CIBULA, Jana DROZENOVA, Pavel FABIAN, Oluwole FADARE, Filip FRUHAUF, Jitka HAUSNEROVÁ, Jan HOJNY, Jan LACO, Sigurd F LAX, Radoslav MATEJ, Gabor MEHES, Romana MICHALKOVA, Kristyna NEMEJCOVA, Naveena SINGH, Simona STOLNICU, Marian SVAJDLER, Tomas ZIMAS, W Glenn MCCLUGGAGE a Vana STRUZINSKA. Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance. PATHOLOGY. AMSTERDAM: ELSEVIER, 2023, roč. 55, č. 6, s. 785-791. ISSN 0031-3025. Dostupné z: https://dx.doi.org/10.1016/j.pathol.2023.04.008.

@article{2360013,
   author = {Dundr, Pavel and Hajkova, Nikola and Bartu Kendall, Michaela and Cibula, David and Drozenova, Jana and Fabian, Pavel and Fadare, Oluwole and Fruhauf, Filip and Hausnerová, Jitka and Hojny, Jan and Laco, Jan and Lax, Sigurd F and Matej, Radoslav and Mehes, Gabor and Michalkova, Romana and Nemejcova, Kristyna and Singh, Naveena and Stolnicu, Simona and Svajdler, Marian and Zimas, Tomas and McCluggage, W Glenn and Struzinska, Vana},
   article_location = {AMSTERDAM},
   article_number = {6},
   doi = {http://dx.doi.org/10.1016/j.pathol.2023.04.008},
   keywords = {Mucinous tumours; ovary; p53; TP53; immunohistochemistry; next generation sequencing},
   language = {eng},
   issn = {0031-3025},
   journal = {PATHOLOGY},
   title = {Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance},
   url = {https://www.sciencedirect.com/science/article/pii/S0031302523001642?via%3Dihub},
   volume = {55},
   year = {2023}
}

TY  - JOUR
ID  - 2360013
AU  - Dundr, Pavel - Hajkova, Nikola - Bartu Kendall, Michaela - Cibula, David - Drozenova, Jana - Fabian, Pavel - Fadare, Oluwole - Fruhauf, Filip - Hausnerová, Jitka - Hojny, Jan - Laco, Jan - Lax, Sigurd F - Matej, Radoslav - Mehes, Gabor - Michalkova, Romana - Nemejcova, Kristyna - Singh, Naveena - Stolnicu, Simona - Svajdler, Marian - Zimas, Tomas - McCluggage, W Glenn - Struzinska, Vana
PY  - 2023
TI  - Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance
JF  - PATHOLOGY
VL  - 55
IS  - 6
SP  - 785-791
EP  - 785-791
PB  - ELSEVIER
SN  - 00313025
KW  - Mucinous tumours
KW  - ovary
KW  - p53
KW  - TP53
KW  - immunohistochemistry
KW  - next generation sequencing
UR  - https://www.sciencedirect.com/science/article/pii/S0031302523001642?via%3Dihub
N2  - 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 aber-rant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tu-mours (strong nuclear p53 staining in >12 consecutive tumour cells) and correlated the results with next genera-tion 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 mu-tation 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 predic-tive 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.
ER  -

DUNDR, Pavel, Nikola HAJKOVA, Michaela BARTU KENDALL, David CIBULA, Jana DROZENOVA, Pavel FABIAN, Oluwole FADARE, Filip FRUHAUF, Jitka HAUSNEROVÁ, Jan HOJNY, Jan LACO, Sigurd F LAX, Radoslav MATEJ, Gabor MEHES, Romana MICHALKOVA, Kristyna NEMEJCOVA, Naveena SINGH, Simona STOLNICU, Marian SVAJDLER, Tomas ZIMAS, W Glenn MCCLUGGAGE a Vana STRUZINSKA. Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance. \textit{PATHOLOGY}. AMSTERDAM: ELSEVIER, 2023, roč.~55, č.~6, s.~785-791. ISSN~0031-3025. Dostupné z: https://dx.doi.org/10.1016/j.pathol.2023.04.008.

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