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Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers.
Breast Cancer Res. 2007; 9(1):R16.BC

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.

Authors+Show Affiliations

Department of Pathology, Seinäjoki Central Hospital, Hanneksenrinne 7, FIN-60220 Seinäjoki, Finland. mervi.jumppanen@epshp.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17263897

Citation

Jumppanen, Mervi, et al. "Basal-like Phenotype Is Not Associated With Patient Survival in Estrogen-receptor-negative Breast Cancers." Breast Cancer Research : BCR, vol. 9, no. 1, 2007, pp. R16.
Jumppanen M, Gruvberger-Saal S, Kauraniemi P, et al. Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers. Breast Cancer Res. 2007;9(1):R16.
Jumppanen, M., Gruvberger-Saal, S., Kauraniemi, P., Tanner, M., Bendahl, P. O., Lundin, M., Krogh, M., Kataja, P., Borg, A., Fernö, M., & Isola, J. (2007). Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers. Breast Cancer Research : BCR, 9(1), R16.
Jumppanen M, et al. Basal-like Phenotype Is Not Associated With Patient Survival in Estrogen-receptor-negative Breast Cancers. Breast Cancer Res. 2007;9(1):R16. PubMed PMID: 17263897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers. AU - Jumppanen,Mervi, AU - Gruvberger-Saal,Sofia, AU - Kauraniemi,Päivikki, AU - Tanner,Minna, AU - Bendahl,Pär-Ola, AU - Lundin,Mikael, AU - Krogh,Morten, AU - Kataja,Pasi, AU - Borg,Ake, AU - Fernö,Mårten, AU - Isola,Jorma, PY - 2006/08/17/received PY - 2006/12/12/revised PY - 2007/01/31/accepted PY - 2007/2/1/pubmed PY - 2007/5/11/medline PY - 2007/2/1/entrez SP - R16 EP - R16 JF - Breast cancer research : BCR JO - Breast Cancer Res VL - 9 IS - 1 N2 - 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. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/17263897/Basal_like_phenotype_is_not_associated_with_patient_survival_in_estrogen_receptor_negative_breast_cancers_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1649 DB - PRIME DP - Unbound Medicine ER -