Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing

Cole, AJ; Dwight, T; Gill, AJ; Dickson, KA; Zhu, Y; Clarkson, A; Gard, GB; Maidens, J; Valmadre, S; Clifton-Bligh, R; Marsh, DJ

Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing

Cole, AJ Dwight, T Gill, AJ Dickson, KA

Zhu, Y Clarkson, A Gard, GB Maidens, J Valmadre, S Clifton-Bligh, R Marsh, DJ

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Publication Type:: Journal Article
Citation:: Scientific Reports, 2016, 6
Issue Date:: 2016-05-18

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Field	Value	Language
dc.contributor.author	Cole, AJ	en_US
dc.contributor.author	Dwight, T	en_US
dc.contributor.author	Gill, AJ	en_US
dc.contributor.author	Dickson, KA https://orcid.org/0000-0001-7307-8982	en_US
dc.contributor.author	Zhu, Y	en_US
dc.contributor.author	Clarkson, A	en_US
dc.contributor.author	Gard, GB	en_US
dc.contributor.author	Maidens, J	en_US
dc.contributor.author	Valmadre, S	en_US
dc.contributor.author	Clifton-Bligh, R	en_US
dc.contributor.author	Marsh, DJ https://orcid.org/0000-0001-5899-4931	en_US
dc.date.available	2016-04-27	en_US
dc.date.issued	2016-05-18	en_US
dc.identifier.citation	Scientific Reports, 2016, 6	en_US
dc.identifier.uri	http://hdl.handle.net/10453/127597
dc.description.abstract	The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as 'Low', 'Intermediate' or 'High' for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression.	en_US
dc.relation.ispartof	Scientific Reports	en_US
dc.relation.isbasedon	10.1038/srep26191	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Ovarian Neoplasms	en_US
dc.subject.mesh	Immunohistochemistry	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Mutation	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Tumor Suppressor Protein p53	en_US
dc.subject.mesh	High-Throughput Nucleotide Sequencing	en_US
dc.title	Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as 'Low', 'Intermediate' or 'High' for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression.

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http://hdl.handle.net/10453/127597