Document Detail

Lymphocyte invasion in IC10/Basal-like breast tumors is associated with wild-type TP53.
MedLine Citation:
PMID:  25351767     Owner:  NLM     Status:  Publisher    
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 pathological 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 ER-negative breast tumors, suggesting a connection between TP53 inactivation and failure of tumor immunosurveillance. Implications: The association of lymphocytic invasion of estrogen receptor-negative breast tumors with the retention of wild-type TP53 implies a novel protective connection between TP53 function and tumor immunosurveillance.
David Quigley; Laxmi Silwal-Pandit; Ruth Dannenfelser; Anita Langerod; Hans Kristian Moen Vollan; Charlie Vaske; Josie Ursini-Siegel; Olga Troyanskaya; Suet-Feung Chin; Carlos Caldas; Allan Balmain; Anne-Lise Borresen-Dale; Vessela Kristensen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-28
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  -     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-29     Completed Date:  -     Revised Date:  2014-10-30    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Association for Cancer Research.
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