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.

Basic information

Original name

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

Authors

DUNDR, Pavel (203 Czech Republic, guarantor), Nikola HAJKOVA (203 Czech Republic), Michaela BARTU KENDALL (203 Czech Republic), David CIBULA (203 Czech Republic), Jana DROZENOVA (203 Czech Republic), Pavel FABIAN (203 Czech Republic), Oluwole FADARE, Filip FRUHAUF (203 Czech Republic), Jitka HAUSNEROVÁ (203 Czech Republic, belonging to the institution), Jan HOJNY (203 Czech Republic), Jan LACO (203 Czech Republic), Sigurd F LAX, Radoslav MATEJ (203 Czech Republic), Gabor MEHES, Romana MICHALKOVA (203 Czech Republic), Kristyna NEMEJCOVA (203 Czech Republic), Naveena SINGH, Simona STOLNICU (203 Czech Republic), Marian SVAJDLER (203 Czech Republic), Tomas ZIMAS (203 Czech Republic), W Glenn MCCLUGGAGE and Vana STRUZINSKA (203 Czech Republic)

Edition

PATHOLOGY, AMSTERDAM, ELSEVIER, 2023, 0031-3025

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30109 Pathology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.500 in 2022

RIV identification code

RIV/00216224:14110/23:00132980

Organization unit

Faculty of Medicine

DOI

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

UT WoS

001082559400001

Keywords in English

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

Abstract

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.

Links

90233, large research infrastructures

Name: 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 and 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, vol. 55, No 6, p. 785-791. ISSN 0031-3025. Available from: 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 and 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, vol.~55, No~6, p.~785-791. ISSN~0031-3025. Available from: https://dx.doi.org/10.1016/j.pathol.2023.04.008.

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