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Keywords {🔍}

tumors, gene, breast, expression, basal, basallike, cancer, pubmed, article, tumor, genes, ernegative, google, scholar, cas, analysis, data, status, ckpositive, cluster, set, cytokeratin, survival, basalphenotype, top, file, cancers, ihc, microarray, immunohistochemically, receptor, signature, classification, list, central, clinical, negative, cells, study, colleagues, figure, subgroup, years, intrinsic, cknegative, prognostic, cell, usa, res, phenotype,

Topics {✒️}

estrogen-receptor-negative breast cancers estrogen-receptor-negative breast tumors distant disease-free survival abd el-rehim dm microarray-analysis-based classifiers agreed estrogen receptor status negative estrogen receptor ck5/ck14/p63 antibody cocktail hypothesis-generating scientific research lymph-node-positive disease superimposed kaplan-meier curves article download pdf er-negative breast cancers abd el-rehim prognostically distinct entity ck5/14-negative tumor groups swiss-prot annotation contained er-negative tumor entity vector-specific primers essentially immunohistochemically predefined ck5/14-positive node-negative invasive carcinomas estrogen receptor full size image reis-filho js erbb2+/er- tumor groups basal cytokeratin-negative tumors er-negative tumor subgroup membrane-bound cellular localization immunohistochemically ck5/14-negative tumors strong er-related signal basal cytokeratin-immunopositive tumors c-kit-expressing tumors basal-phenotype breast cancer van de rijn basal cytokeratin-positive tumors ck5/14-negative tumors categorized genome-wide expression patterns immunohistochemically ck5/14-positive tumors microarray-based gene data estrogen-positive tumors gene-expression-based classification basal er-negative tumors basal-phenotype breast tumors malignant breast disease seinäjoki central hospital hormone receptor analysis poorly measured/expressed spots human breast carcinoma additional ck5/14-negative tumors misclassified ck5/14-negative tumors

Questions {❓}

• Birmbaum D, Bertucci F, Ginestier C, Tagett R, Jacquemier J, Charafe-Jauffret E: Basal and luminal breast cancer: basic or luminous?
• Korsching E, Packeisen J, Liedtke C, Hungermann D, Wulfing P, van Diest PJ, Brandt P, Boecker W, Buerger H: The origin of vimentin expression in invasive breast cancer: epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential?

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         headline:Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers
         description: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. 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. 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. 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.
         datePublished:2007-01-31T00:00:00Z
         dateModified:2007-01-31T00:00:00Z
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            Estrogen Receptor Status
            Basal Cytokeratin
            Negative Estrogen Receptor Status
            Receptor Protein Signaling Pathway
            Distinct Gene Expression Signature
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers
      description: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. 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. 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. 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.
      datePublished:2007-01-31T00:00:00Z
      dateModified:2007-01-31T00:00:00Z
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      pageEnd:10
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         Estrogen Receptor Status
         Basal Cytokeratin
         Negative Estrogen Receptor Status
         Receptor Protein Signaling Pathway
         Distinct Gene Expression Signature
         Cancer Research
         Oncology
         Surgical Oncology
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      name:Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland
      name:Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland
      name:Department of Oncology, Tampere University Hospital, Tampere, Finland
      name:Department of Oncology, Clinical Sciences, University of Lund, Lund, Sweden
      name:Biomedical Informatics group, Department of Oncology, University of Helsinki, Helsinki, Finland
      name:Department of Theoretical Physics, Lund University, Lund, Sweden
      name:Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland
      name:Department of Oncology, Clinical Sciences, University of Lund, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, University of Lund, Lund, Sweden
      name:Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland

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