Pan-cancer analysis of p53 immunohistochemical staining

Gerald Li, Richard Turkington, Philip Dunne, David Boyle, Gareth Irwin, Jacqueline James, Manuel Salto-Tellez, Darragh McArt, Peter Hamilton

Research output: Other contribution

Abstract

Cancer is a disease of genetic dysregulation. It is little wonder, then, that p53, which plays a central role in regulating the cell’s response to DNA damage, is one of the most frequently mutated genes across many cancer types. Normal, healthy cells constitutively express low levels of p53, detectable immunohistochemically as weak staining rather than complete negativity. However, previous work has shown that in breast cancer, extreme positive or negative staining for p53 were both correlated with worse overall survival and p53 mutation when compared to cases with weak p53 staining. This extreme expression phenotype may serve as a simple and cost-effective biomarker for p53 mutation and poor prognosis in breast cancer, but it remains unclear how applicable it may be to other cancer types. While p53 mutation is common across many cancer types, mutation rates vary greatly, implying potential differences in the underlying biology. In this study, we tried to replicate the extreme expression analysis of p53 staining across multiple cancer types to see whether this could be a part of a universal biomarker of cancer or if instead there are fundamental differences in p53 biology between different cancer types. Leveraging our framework for integrated, multimodal biomarker discovery and validation, Pathology Integromics in Cancer (PICan), we found that similar correlations between p53 extreme expression and survival might be found in other cancer types as well. Further work will be needed to verify whether the same underlying biochemistry is at play.
Original languageEnglish
PublisherFaculty of Medicine, Health and Life Sciences Postdoc Society
Place of PublicationBelfast, UK
Publication statusPublished - 2016

Publication series

NameFaculty of Medicine, Health and Life Sciences Postdoc Society Annual Symposium

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Staining and Labeling
Neoplasms
Mutation
Biomarkers
Breast Neoplasms
Negative Staining
Inborn Genetic Diseases
Mutation Rate
Tumor Biomarkers
Biochemistry
DNA Damage
Pathology
Phenotype
Costs and Cost Analysis
Genes

Cite this

Li, G., Turkington, R., Dunne, P., Boyle, D., Irwin, G., James, J., ... Hamilton, P. (2016). Pan-cancer analysis of p53 immunohistochemical staining. Belfast, UK: Faculty of Medicine, Health and Life Sciences Postdoc Society.
Li, Gerald ; Turkington, Richard ; Dunne, Philip ; Boyle, David ; Irwin, Gareth ; James, Jacqueline ; Salto-Tellez, Manuel ; McArt, Darragh ; Hamilton, Peter. / Pan-cancer analysis of p53 immunohistochemical staining. 2016. Belfast, UK : Faculty of Medicine, Health and Life Sciences Postdoc Society. (Faculty of Medicine, Health and Life Sciences Postdoc Society Annual Symposium).
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Li, G, Turkington, R, Dunne, P, Boyle, D, Irwin, G, James, J, Salto-Tellez, M, McArt, D & Hamilton, P 2016, Pan-cancer analysis of p53 immunohistochemical staining. Faculty of Medicine, Health and Life Sciences Postdoc Society, Belfast, UK.

Pan-cancer analysis of p53 immunohistochemical staining. / Li, Gerald; Turkington, Richard; Dunne, Philip; Boyle, David; Irwin, Gareth; James, Jacqueline; Salto-Tellez, Manuel; McArt, Darragh; Hamilton, Peter.

Belfast, UK : Faculty of Medicine, Health and Life Sciences Postdoc Society. 2016, . (Faculty of Medicine, Health and Life Sciences Postdoc Society Annual Symposium).

Research output: Other contribution

TY - GEN

T1 - Pan-cancer analysis of p53 immunohistochemical staining

AU - Li, Gerald

AU - Turkington, Richard

AU - Dunne, Philip

AU - Boyle, David

AU - Irwin, Gareth

AU - James, Jacqueline

AU - Salto-Tellez, Manuel

AU - McArt, Darragh

AU - Hamilton, Peter

PY - 2016

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N2 - Cancer is a disease of genetic dysregulation. It is little wonder, then, that p53, which plays a central role in regulating the cell’s response to DNA damage, is one of the most frequently mutated genes across many cancer types. Normal, healthy cells constitutively express low levels of p53, detectable immunohistochemically as weak staining rather than complete negativity. However, previous work has shown that in breast cancer, extreme positive or negative staining for p53 were both correlated with worse overall survival and p53 mutation when compared to cases with weak p53 staining. This extreme expression phenotype may serve as a simple and cost-effective biomarker for p53 mutation and poor prognosis in breast cancer, but it remains unclear how applicable it may be to other cancer types. While p53 mutation is common across many cancer types, mutation rates vary greatly, implying potential differences in the underlying biology. In this study, we tried to replicate the extreme expression analysis of p53 staining across multiple cancer types to see whether this could be a part of a universal biomarker of cancer or if instead there are fundamental differences in p53 biology between different cancer types. Leveraging our framework for integrated, multimodal biomarker discovery and validation, Pathology Integromics in Cancer (PICan), we found that similar correlations between p53 extreme expression and survival might be found in other cancer types as well. Further work will be needed to verify whether the same underlying biochemistry is at play.

AB - Cancer is a disease of genetic dysregulation. It is little wonder, then, that p53, which plays a central role in regulating the cell’s response to DNA damage, is one of the most frequently mutated genes across many cancer types. Normal, healthy cells constitutively express low levels of p53, detectable immunohistochemically as weak staining rather than complete negativity. However, previous work has shown that in breast cancer, extreme positive or negative staining for p53 were both correlated with worse overall survival and p53 mutation when compared to cases with weak p53 staining. This extreme expression phenotype may serve as a simple and cost-effective biomarker for p53 mutation and poor prognosis in breast cancer, but it remains unclear how applicable it may be to other cancer types. While p53 mutation is common across many cancer types, mutation rates vary greatly, implying potential differences in the underlying biology. In this study, we tried to replicate the extreme expression analysis of p53 staining across multiple cancer types to see whether this could be a part of a universal biomarker of cancer or if instead there are fundamental differences in p53 biology between different cancer types. Leveraging our framework for integrated, multimodal biomarker discovery and validation, Pathology Integromics in Cancer (PICan), we found that similar correlations between p53 extreme expression and survival might be found in other cancer types as well. Further work will be needed to verify whether the same underlying biochemistry is at play.

M3 - Other contribution

T3 - Faculty of Medicine, Health and Life Sciences Postdoc Society Annual Symposium

PB - Faculty of Medicine, Health and Life Sciences Postdoc Society

CY - Belfast, UK

ER -