[HTML][HTML] Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas

B Kreike, M van Kouwenhove, H Horlings… - Breast Cancer …, 2007 - Springer
B Kreike, M van Kouwenhove, H Horlings, B Weigelt, H Peterse, H Bartelink
Breast Cancer Research, 2007Springer
Introduction Breast cancer is a heterogeneous group of tumors, and can be subdivided on
the basis of histopathological features, genetic alterations and gene-expression profiles.
One well-defined subtype of breast cancer is characterized by a lack of HER2 gene
amplification and estrogen and progesterone receptor expression ('triple-negative tumors').
We examined the histopathological and gene-expression profile of triple-negative tumors to
define subgroups with specific characteristics, including risk of developing distant …
Introduction
Breast cancer is a heterogeneous group of tumors, and can be subdivided on the basis of histopathological features, genetic alterations and gene-expression profiles. One well-defined subtype of breast cancer is characterized by a lack of HER2 gene amplification and estrogen and progesterone receptor expression ('triple-negative tumors'). We examined the histopathological and gene-expression profile of triple-negative tumors to define subgroups with specific characteristics, including risk of developing distant metastases.
Methods
97 triple-negative tumors were selected from the fresh-frozen tissue bank of the Netherlands Cancer Institute, and gene-expression profiles were generated using 35K oligonucleotide microarrays. In addition, histopathological and immunohistochemical characterization was performed, and the findings were associated to clinical features.
Results
All triple-negative tumors were classified as basal-like tumors on the basis of their overall gene-expression profile. Hierarchical cluster analysis revealed five distinct subgroups of triple-negative breast cancers. Multivariable analysis showed that a large amount of lymphocytic infiltrate (HR = 0.30, 95% CI 0.09–0.96) and absence of central fibrosis in the tumors (HR = 0.14, 95% CI 0.03–0.62) were associated with distant metastasis-free survival.
Conclusion
Triple-negative tumors are synonymous with basal-like tumors, and can be identified by immunohistochemistry. Based on gene-expression profiling, basal-like tumors are still heterogeneous and can be subdivided into at least five distinct subgroups. The development of distant metastasis in basal-like tumors is associated with the presence of central fibrosis and a small amount of lymphocytic infiltrate.
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