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Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer.

Deb, Siddhartha; Johansson, Ida LU ; Byrne, David; Nilsson, Cecilia; Investigators, Kconfab; Constable, Leonie; Fjällskog, Marie-Louise; Dobrovic, Alexander; Hedenfalk, Ingrid LU and Fox, Stephen B (2014) In Modern Pathology 27(9). p.1223-1230
Abstract
Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1α (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the... (More)
Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1α (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.Modern Pathology advance online publication, 24 January 2014; doi:10.1038/modpathol.2013.231. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
Modern Pathology
volume
27
issue
9
pages
1223 - 1230
publisher
Nature Publishing Group
external identifiers
  • pmid:24457463
  • wos:000341620100005
  • scopus:84925228811
ISSN
1530-0285
DOI
10.1038/modpathol.2013.231
language
English
LU publication?
yes
id
36bd5d8c-d1c2-49ee-a781-8ec4926e28d0 (old id 4290759)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24457463?dopt=Abstract
date added to LUP
2014-02-07 14:11:22
date last changed
2017-10-08 03:19:15
@article{36bd5d8c-d1c2-49ee-a781-8ec4926e28d0,
  abstract     = {Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1α (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.Modern Pathology advance online publication, 24 January 2014; doi:10.1038/modpathol.2013.231.},
  author       = {Deb, Siddhartha and Johansson, Ida and Byrne, David and Nilsson, Cecilia and Investigators, Kconfab and Constable, Leonie and Fjällskog, Marie-Louise and Dobrovic, Alexander and Hedenfalk, Ingrid and Fox, Stephen B},
  issn         = {1530-0285},
  language     = {eng},
  number       = {9},
  pages        = {1223--1230},
  publisher    = {Nature Publishing Group},
  series       = {Modern Pathology},
  title        = {Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer.},
  url          = {http://dx.doi.org/10.1038/modpathol.2013.231},
  volume       = {27},
  year         = {2014},
}