Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma

Puk Meijs-Hermanns; Henrica M.J. Werner; Loes Kooreman; Petra Bretová; Vit Weinberger; Stephanie Vrede; Luthy S.M. Alcala; Frédéric Amant; Jasmin Asberger; Markéta Bednaríková; Dorry Boll; Carolien M. Bronkhorst; Johan Bulten; Antonio Gil-Moreno; Ingfrid S. Haldorsen; Jitka Hausnerová; Jutta Huvila; Martin Koskas; Camilla Krakstad; Heidi Küsters-Vandevelde; Gemma Mancebo Moreno; Xavier Matias-Guiu; Huy Ngo; Brenda M. Pijlman; Maria Santacana; Marieke Smink; Jone Trovik; Viola M.J. Verhoef; Koen Van de Vijver; Dennis van Hamont; Anneke A.M. van der Wurff; Johanna M.A. Pijnenborg; Nicole C.M. Visser

doi:10.1016/j.ijgc.2025.101682

Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma

Puk Meijs-Hermanns, Henrica M.J. Werner^*, Loes Kooreman, Petra Bretová, Vit Weinberger, Stephanie Vrede, Luthy S.M. Alcala, Frédéric Amant, Jasmin Asberger, Markéta Bednaríková, Dorry Boll, Carolien M. Bronkhorst, Johan Bulten, Antonio Gil-Moreno, Ingfrid S. Haldorsen, Jitka Hausnerová, Jutta Huvila, Martin Koskas, Camilla Krakstad, Heidi Küsters-VandeveldeGemma Mancebo Moreno, Xavier Matias-Guiu, Huy Ngo, Brenda M. Pijlman, Maria Santacana, Marieke Smink, Jone Trovik, Viola M.J. Verhoef, Koen Van de Vijver, Dennis van Hamont, Anneke A.M. van der Wurff, Johanna M.A. Pijnenborg, Nicole C.M. Visser

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Methods: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. Results: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. Conclusions: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

Original language	English
Article number	101682
Journal	International Journal of Gynecological Cancer
Volume	35
Issue number	4
DOIs	https://doi.org/10.1016/j.ijgc.2025.101682
Publication status	E-pub ahead of print - 1 Jan 2025

Keywords

Endometrioid Endometrial Carcinoma
Grade 2
p53
Progesterone Receptor

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Meijs-Hermanns, P., Werner, H. M. J., Kooreman, L., Bretová, P., Weinberger, V., Vrede, S., Alcala, L. S. M., Amant, F., Asberger, J., Bednaríková, M., Boll, D., Bronkhorst, C. M., Bulten, J., Gil-Moreno, A., Haldorsen, I. S., Hausnerová, J., Huvila, J., Koskas, M., Krakstad, C., ... Visser, N. C. M. (2025). Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma. International Journal of Gynecological Cancer, 35(4), Article 101682. Advance online publication. https://doi.org/10.1016/j.ijgc.2025.101682

@article{0e7d23154e33467eaada06899852d993,

title = "Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma",

abstract = "Objective: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Methods: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. Results: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8\% vs 97.5\%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5\%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. Conclusions: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.",

keywords = "Endometrioid Endometrial Carcinoma, Grade 2, p53, Progesterone Receptor",

author = "Puk Meijs-Hermanns and Werner, \{Henrica M.J.\} and Loes Kooreman and Petra Bretov{\'a} and Vit Weinberger and Stephanie Vrede and Alcala, \{Luthy S.M.\} and Fr{\'e}d{\'e}ric Amant and Jasmin Asberger and Mark{\'e}ta Bednar{\'i}kov{\'a} and Dorry Boll and Bronkhorst, \{Carolien M.\} and Johan Bulten and Antonio Gil-Moreno and Haldorsen, \{Ingfrid S.\} and Jitka Hausnerov{\'a} and Jutta Huvila and Martin Koskas and Camilla Krakstad and Heidi K{\"u}sters-Vandevelde and \{Mancebo Moreno\}, Gemma and Xavier Matias-Guiu and Huy Ngo and Pijlman, \{Brenda M.\} and Maria Santacana and Marieke Smink and Jone Trovik and Verhoef, \{Viola M.J.\} and Vijver, \{Koen Van de\} and Hamont, \{Dennis van\} and \{van der Wurff\}, \{Anneke A.M.\} and Pijnenborg, \{Johanna M.A.\} and Visser, \{Nicole C.M.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = jan,

day = "1",

doi = "10.1016/j.ijgc.2025.101682",

language = "English",

volume = "35",

journal = "International Journal of Gynecological Cancer",

issn = "1048-891X",

publisher = "Elsevier Inc.",

number = "4",

}

Meijs-Hermanns, P, Werner, HMJ , Kooreman, L, Bretová, P, Weinberger, V, Vrede, S, Alcala, LSM, Amant, F, Asberger, J, Bednaríková, M, Boll, D, Bronkhorst, CM, Bulten, J, Gil-Moreno, A, Haldorsen, IS, Hausnerová, J, Huvila, J, Koskas, M, Krakstad, C, Küsters-Vandevelde, H, Mancebo Moreno, G, Matias-Guiu, X, Ngo, H, Pijlman, BM, Santacana, M, Smink, M, Trovik, J, Verhoef, VMJ, Vijver, KVD, Hamont, DV, van der Wurff, AAM, Pijnenborg, JMA & Visser, NCM 2025, 'Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma', International Journal of Gynecological Cancer, vol. 35, no. 4, 101682. https://doi.org/10.1016/j.ijgc.2025.101682

TY - JOUR

T1 - Improving pre-operative binary grading

T2 - relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma

AU - Meijs-Hermanns, Puk

AU - Werner, Henrica M.J.

AU - Kooreman, Loes

AU - Bretová, Petra

AU - Weinberger, Vit

AU - Vrede, Stephanie

AU - Alcala, Luthy S.M.

AU - Amant, Frédéric

AU - Asberger, Jasmin

AU - Bednaríková, Markéta

AU - Boll, Dorry

AU - Bronkhorst, Carolien M.

AU - Bulten, Johan

AU - Gil-Moreno, Antonio

AU - Haldorsen, Ingfrid S.

AU - Hausnerová, Jitka

AU - Huvila, Jutta

AU - Koskas, Martin

AU - Krakstad, Camilla

AU - Küsters-Vandevelde, Heidi

AU - Mancebo Moreno, Gemma

AU - Matias-Guiu, Xavier

AU - Ngo, Huy

AU - Pijlman, Brenda M.

AU - Santacana, Maria

AU - Smink, Marieke

AU - Trovik, Jone

AU - Verhoef, Viola M.J.

AU - Vijver, Koen Van de

AU - Hamont, Dennis van

AU - van der Wurff, Anneke A.M.

AU - Pijnenborg, Johanna M.A.

AU - Visser, Nicole C.M.

PY - 2025/1/1

Y1 - 2025/1/1

N2 - Objective: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Methods: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. Results: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. Conclusions: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

AB - Objective: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Methods: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. Results: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. Conclusions: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

KW - Endometrioid Endometrial Carcinoma

KW - Grade 2

KW - p53

KW - Progesterone Receptor

U2 - 10.1016/j.ijgc.2025.101682

DO - 10.1016/j.ijgc.2025.101682

M3 - Article

SN - 1048-891X

VL - 35

JO - International Journal of Gynecological Cancer

JF - International Journal of Gynecological Cancer

IS - 4

M1 - 101682

ER -

Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma

Abstract

Keywords

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