title: Lymphocyte Invasion in IC10/Basal-Like Breast Tumors Is Associated with Wild-Type TP53.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Quigley
authors.affiliation: 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.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Silwal-Pandit
authors.affiliation: Department of Computer Science, Princeton University, Princeton New Jersey. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dannenfelser
authors.affiliation: 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.
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.affiliation: 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.
authors.forename: Hans Kristian Moen
authors.initials: HK
authors.lastname: Vollan
authors.affiliation: Five3 Genomics, Inc., Santa Cruz, California.
authors.forename: Charles
authors.initials: C
authors.lastname: Vaske
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Québec, Canada.
authors.forename: Josie Ursini
authors.initials: JU
authors.lastname: Siegel
authors.affiliation: Department of Computer Science, Princeton University, Princeton New Jersey. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
authors.forename: Olga
authors.initials: O
authors.lastname: Troyanskaya
authors.affiliation: Cancer Research UK, Cambridge Institute and Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Suet-Feung
authors.initials: SF
authors.lastname: Chin
authors.affiliation: 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.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California.
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
authors.affiliation: 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.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: 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.
authors.forename: Vessela
authors.initials: V
authors.lastname: Kristensen
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D015415:Biomarkers; D011960:Receptors, Estrogen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53