Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers

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dc.contributor.author Gruvberger-Saal, Sofia -
dc.contributor.author Bendahl, Pär-Ola -
dc.contributor.author Lundin, Mikael -
dc.contributor.author Jumppanen, Mervi (Tay) -
dc.contributor.author Kauraniemi, Päivikki (Tay) -
dc.contributor.author Tanner, Minna (Tay) -
dc.contributor.author Kataja, Pasi (Tay) -
dc.contributor.author Isola, Jorma (Tay) -
dc.date.accessioned 2012-06-17T20:14:05Z
dc.date.available 2012-06-17 09:17:42 -
dc.date.available 2012-06-17T20:14:05Z
dc.date.issued 2007 -
dc.identifier.issn 1465-542X -
dc.identifier.uri http://tampub.uta.fi/handle/10024/65853
dc.description BioMed Central Open access -
dc.description.abstract Introduction Basal-phenotype or basal-like breast cancers are characterized by basal epithelium cytokeratin (CK5/14/17) expression, negative estrogen receptor (ER) status and distinct gene expression signature. We studied the clinical and biological features of the basal-phenotype tumors determined by immunohistochemistry (IHC) and cDNA microarrays especially within the ER-negative subgroup. Methods IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers. The gene expression signature of the CK5/14 immunopositive tumors was investigated within a subset (100) of the breast tumors (including 50 ER-negative tumors) with a cDNA microarray. Survival for basal-phenotype tumors as determined by CK5/14 IHC and gene expression signature was assessed. Results From the 375 analyzable tumor specimens, 48 (13%) were immunohistochemically positive for CK5/14. We found adverse distant disease-free survival for the CK5/14-positive tumors during the first years (3 years hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.17 to 4.24, p = 0.01; 5 years HR 1.80, 95% CI 1.02 to 3.15, p = 0.04) but the significance was lost at the end of the follow-up period (10 years HR 1.43, 95% CI 0.84 to 2.43, p = 0.19). Gene expression profiles of immunohistochemically determined CK5/14-positive tumors within the ER-negative tumor group implicated 1,713 differently expressed genes (p < 0.05). Hierarchical clustering analysis with the top 500 of these genes formed one basal-like and a non-basal-like cluster also within the ER-negative tumor entity. A highly concordant classification could be constructed with a published gene set (Sorlie's intrinsic gene set, concordance 90%). Both gene sets identified a basal-like cluster that included most of the CK5/14-positive tumors, but also immunohistochemically CK5/14-negative tumors. Within the ER-negative tumor entity there was no survival difference between the non-basal and basal-like tumors as identified by immunohistochemical or gene-expression-based classification. Conclusion Basal cytokeratin-positive tumors have a biologically distinct gene expression signature from other ER-negative tumors. Even if basal cytokeratin expression predicts early relapse among non-selected tumors, the clinical outcome of basal tumors is similar to non-basal ER-negative tumors. Immunohistochemically basal cytokeratin-positive tumors almost always belong to the basal-like gene expression profile, but this cluster also includes few basal cytokeratin-negative tumors. -
dc.language.iso en -
dc.title Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-615 -
dc.identifier.doi 10.1186/bcr1649 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Lääketieteen bioteknologia | en=Medical biotechnology| -
dc.journal.title Breast Cancer Research -
dc.journal.volume 9 -
dc.journal.number R16 -
dc.journal.volumepagerange 1-10 -
dc.oldstats 51 -

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