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Nuclear HIF1A expre...
Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer
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Deb, Siddhartha (author)
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- Johansson, Ida (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Byrne, David (author)
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- Nilsson, Cecilia (author)
- Uppsala universitet,Centrum för klinisk forskning, Västerås
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Constable, Leonie (author)
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- Fjällskog, Marie-Louise (author)
- Uppsala universitet,Enheten för onkologi
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Dobrovic, Alexander (author)
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- Hedenfalk, Ingrid (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Fox, Stephen B. (author)
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Investigators, Kconfab (author)
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- English.
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In: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 27:9, s. 1223-1230
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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-1 alpha (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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- BRCA1
- BRCA2
- BRCAX
- CA9
- familial
- HIF1A
- male breast cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Deb, Siddhartha
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Johansson, Ida
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Byrne, David
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Nilsson, Cecilia
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Constable, Leoni ...
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Fjällskog, Marie ...
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show more...
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Dobrovic, Alexan ...
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Hedenfalk, Ingri ...
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Fox, Stephen B.
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Investigators, K ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Modern Pathology
- By the university
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Uppsala University
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Lund University