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Mol Cancer Res. 2015 Mar;13(3):493-501. doi: 10.1158/1541-7786.MCR-14-0387. Epub 2014 Oct 28.

Lymphocyte Invasion in IC10/Basal-Like Breast Tumors Is Associated with Wild-Type TP53.

Author information

1
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California.
2
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
3
Department of Computer Science, Princeton University, Princeton New Jersey. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
4
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
5
Five3 Genomics, Inc., Santa Cruz, California.
6
Lady Davis Institute for Medical Research, Montreal, Québec, Canada.
7
Cancer Research UK, Cambridge Institute and Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
8
Cancer Research UK, Cambridge Institute and Department of Oncology, University of Cambridge, Cambridge, United Kingdom. Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation, Trust and NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom. Cambridge Experimental Cancer Medicine Centre, Cambridge, United Kingdom.
9
Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California.
10
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. v.n.kristensen@medisin.uio.no a.l.borresen-dale@medisin.uio.no.
11
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Department of Clinical Molecular Oncology, Division of Medicine, Akershus University Hospital, Ahus, Norway. v.n.kristensen@medisin.uio.no a.l.borresen-dale@medisin.uio.no.

Abstract

Lymphocytic infiltration is associated with better prognosis in several epithelial malignancies including breast cancer. The tumor suppressor TP53 is mutated in approximately 30% of breast adenocarcinomas, with varying frequency across molecular subtypes. In this study of 1,420 breast tumors, we tested for interaction between TP53 mutation status and tumor subtype determined by PAM50 and integrative cluster analysis. In integrative cluster 10 (IC10)/basal-like breast cancer, we identify an association between lymphocytic infiltration, determined by an expression score, and retention of wild-type TP53. The expression-derived score agreed with the degree of lymphocytic infiltration assessed by pathologic review, and application of the Nanodissect algorithm was suggestive of this infiltration being primarily of cytotoxic T lymphocytes (CTL). Elevated expression of this CTL signature was associated with longer survival in IC10/Basal-like tumors. These findings identify a new link between the TP53 pathway and the adaptive immune response in estrogen receptor (ER)-negative breast tumors, suggesting a connection between TP53 inactivation and failure of tumor immunosurveillance.

IMPLICATIONS:

The association of lymphocytic invasion of ER-negative breast tumors with the retention of wild-type TP53 implies a novel protective connection between TP53 function and tumor immunosurveillance.

PMID:
25351767
PMCID:
PMC4465579
DOI:
10.1158/1541-7786.MCR-14-0387
[Indexed for MEDLINE]
Free PMC Article

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