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

Jumppanen M, Gruvberger-Saal S, Kauraniemi P, Tanner M, Bendahl PO, Lundin M, Krogh M, Kataja P, Borg A, Fernö M, Isola J - Breast Cancer Res. (2007)

Bottom Line: 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.IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers.A highly concordant classification could be constructed with a published gene set (Sorlie's intrinsic gene set, concordance 90%).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Seinäjoki Central Hospital, Hanneksenrinne 7, FIN-60220 Seinäjoki, Finland. mervi.jumppanen@epshp.fi

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.

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Distant disease-free survival of immunohistochemically CK5/14-negative and CK5/14-positive tumors in the whole data set. The basal cytokeratin-positive tumors show significantly shorter survival during the first years of the follow-up, but this difference is lost with time.
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Figure 3: Distant disease-free survival of immunohistochemically CK5/14-negative and CK5/14-positive tumors in the whole data set. The basal cytokeratin-positive tumors show significantly shorter survival during the first years of the follow-up, but this difference is lost with time.

Mentions: Association of the basal status with patient prognosis was evaluated first in the immunohistochemically defined basal (CK5/14-positive) and non-basal (CK5/14-negative) tumor subgroups. In the whole tumor material, the distant disease-free survival was significantly shorter for the CK5/14-positive tumors during the first years of follow-up (3 years hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.17 to 4.24, p = 0.01 and 5 years HR 1.80, 95% CI 1.02 to 3.15, p = 0.04), but this difference 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; Figure 3). Next we studied clinical outcome within the ER-negative entity. The survival rates of immunohistochemically CK5/14-positive and CK5/14-negative tumor groups were identical, as demonstrated by the superimposed Kaplan-Meier curves and log-rank test (p = 0.93; Figure 4a). The same result was obtained when the basal-like classification was based on gene expression microarrays (p = 0.42 and p = 0.55 for classifications based on our gene list and Sorlie's gene list (Figure 4b,c), respectively).


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

Jumppanen M, Gruvberger-Saal S, Kauraniemi P, Tanner M, Bendahl PO, Lundin M, Krogh M, Kataja P, Borg A, Fernö M, Isola J - Breast Cancer Res. (2007)

Distant disease-free survival of immunohistochemically CK5/14-negative and CK5/14-positive tumors in the whole data set. The basal cytokeratin-positive tumors show significantly shorter survival during the first years of the follow-up, but this difference is lost with time.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851391&req=5

Figure 3: Distant disease-free survival of immunohistochemically CK5/14-negative and CK5/14-positive tumors in the whole data set. The basal cytokeratin-positive tumors show significantly shorter survival during the first years of the follow-up, but this difference is lost with time.
Mentions: Association of the basal status with patient prognosis was evaluated first in the immunohistochemically defined basal (CK5/14-positive) and non-basal (CK5/14-negative) tumor subgroups. In the whole tumor material, the distant disease-free survival was significantly shorter for the CK5/14-positive tumors during the first years of follow-up (3 years hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.17 to 4.24, p = 0.01 and 5 years HR 1.80, 95% CI 1.02 to 3.15, p = 0.04), but this difference 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; Figure 3). Next we studied clinical outcome within the ER-negative entity. The survival rates of immunohistochemically CK5/14-positive and CK5/14-negative tumor groups were identical, as demonstrated by the superimposed Kaplan-Meier curves and log-rank test (p = 0.93; Figure 4a). The same result was obtained when the basal-like classification was based on gene expression microarrays (p = 0.42 and p = 0.55 for classifications based on our gene list and Sorlie's gene list (Figure 4b,c), respectively).

Bottom Line: 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.IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers.A highly concordant classification could be constructed with a published gene set (Sorlie's intrinsic gene set, concordance 90%).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Seinäjoki Central Hospital, Hanneksenrinne 7, FIN-60220 Seinäjoki, Finland. mervi.jumppanen@epshp.fi

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.

Show MeSH
Related in: MedlinePlus