Publication

Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative

Edmondson, R. J., Crosbie, E. J., Nickkho-Amiry, M., Kaufmann, A., Stelloo, E., Nijman, H. W., Leary, A., Auguste, A., Mileshkin, L., Pollock, P., MacKay, H. J., Powell, M. E., Bosse, T., Creutzberg, C. L. & Kitchener, H. C., Aug-2017, In : Gynecologic Oncology. 146, 2, p. 327-333 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Edmondson, R. J., Crosbie, E. J., Nickkho-Amiry, M., Kaufmann, A., Stelloo, E., Nijman, H. W., Leary, A., Auguste, A., Mileshkin, L., Pollock, P., MacKay, H. J., Powell, M. E., Bosse, T., Creutzberg, C. L., & Kitchener, H. C. (2017). Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative. Gynecologic Oncology, 146(2), 327-333. https://doi.org/10.1016/j.ygyno.2017.05.014

Author

Edmondson, R. J. ; Crosbie, E. J. ; Nickkho-Amiry, M. ; Kaufmann, A. ; Stelloo, E. ; Nijman, H. W. ; Leary, A. ; Auguste, A. ; Mileshkin, L. ; Pollock, P. ; MacKay, H. J. ; Powell, M. E. ; Bosse, T. ; Creutzberg, C. L. ; Kitchener, H. C. / Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer : A TransPORTEC initiative. In: Gynecologic Oncology. 2017 ; Vol. 146, No. 2. pp. 327-333.

Harvard

Edmondson, RJ, Crosbie, EJ, Nickkho-Amiry, M, Kaufmann, A, Stelloo, E, Nijman, HW, Leary, A, Auguste, A, Mileshkin, L, Pollock, P, MacKay, HJ, Powell, ME, Bosse, T, Creutzberg, CL & Kitchener, HC 2017, 'Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative', Gynecologic Oncology, vol. 146, no. 2, pp. 327-333. https://doi.org/10.1016/j.ygyno.2017.05.014

Standard

Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer : A TransPORTEC initiative. / Edmondson, R. J.; Crosbie, E. J.; Nickkho-Amiry, M.; Kaufmann, A.; Stelloo, E.; Nijman, H. W.; Leary, A.; Auguste, A.; Mileshkin, L.; Pollock, P.; MacKay, H. J.; Powell, M. E.; Bosse, T.; Creutzberg, C. L.; Kitchener, H. C.

In: Gynecologic Oncology, Vol. 146, No. 2, 08.2017, p. 327-333.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Edmondson RJ, Crosbie EJ, Nickkho-Amiry M, Kaufmann A, Stelloo E, Nijman HW et al. Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative. Gynecologic Oncology. 2017 Aug;146(2):327-333. https://doi.org/10.1016/j.ygyno.2017.05.014


BibTeX

@article{8588d5760286403b80786b1897fc7fdf,
title = "Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative",
abstract = "Background. The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway.Methods. We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63.Results. About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% C1237-7.27) and 7.48 (95% C13.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed.Conclusion. Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.",
keywords = "Endometrial cancer, Molecular profiling, Prognosis, p53, p21, pp63, L1CAM, Pole, P63, PROGNOSIS, CLASSIFICATION, EXPRESSION, CARCINOMA, WORKING",
author = "Edmondson, {R. J.} and Crosbie, {E. J.} and M. Nickkho-Amiry and A. Kaufmann and E. Stelloo and Nijman, {H. W.} and A. Leary and A. Auguste and L. Mileshkin and P. Pollock and MacKay, {H. J.} and Powell, {M. E.} and T. Bosse and Creutzberg, {C. L.} and Kitchener, {H. C.}",
note = "Copyright {\textcopyright} 2017. Published by Elsevier Inc.",
year = "2017",
month = aug,
doi = "10.1016/j.ygyno.2017.05.014",
language = "English",
volume = "146",
pages = "327--333",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
number = "2",

}

RIS

TY - JOUR

T1 - Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer

T2 - A TransPORTEC initiative

AU - Edmondson, R. J.

AU - Crosbie, E. J.

AU - Nickkho-Amiry, M.

AU - Kaufmann, A.

AU - Stelloo, E.

AU - Nijman, H. W.

AU - Leary, A.

AU - Auguste, A.

AU - Mileshkin, L.

AU - Pollock, P.

AU - MacKay, H. J.

AU - Powell, M. E.

AU - Bosse, T.

AU - Creutzberg, C. L.

AU - Kitchener, H. C.

N1 - Copyright © 2017. Published by Elsevier Inc.

PY - 2017/8

Y1 - 2017/8

N2 - Background. The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway.Methods. We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63.Results. About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% C1237-7.27) and 7.48 (95% C13.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed.Conclusion. Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.

AB - Background. The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway.Methods. We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63.Results. About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% C1237-7.27) and 7.48 (95% C13.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed.Conclusion. Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.

KW - Endometrial cancer

KW - Molecular profiling

KW - Prognosis

KW - p53

KW - p21

KW - pp63

KW - L1CAM

KW - Pole

KW - P63

KW - PROGNOSIS

KW - CLASSIFICATION

KW - EXPRESSION

KW - CARCINOMA

KW - WORKING

U2 - 10.1016/j.ygyno.2017.05.014

DO - 10.1016/j.ygyno.2017.05.014

M3 - Article

C2 - 28511869

VL - 146

SP - 327

EP - 333

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -

ID: 46861159