[HTML][HTML] Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer

A Prat, JS Parker, O Karginova, C Fan, C Livasy… - Breast cancer …, 2010 - Springer
A Prat, JS Parker, O Karginova, C Fan, C Livasy, JI Herschkowitz, X He, CM Perou
Breast cancer research, 2010Springer
Introduction In breast cancer, gene expression analyses have defined five tumor subtypes
(luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has
unique biologic and prognostic features. Here, we comprehensively characterize the
recently identified claudin-low tumor subtype. Methods The clinical, pathological and
biological features of claudin-low tumors were compared to the other tumor subtypes using
an updated human tumor database and multiple independent data sets. These main …
Introduction
In breast cancer, gene expression analyses have defined five tumor subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has unique biologic and prognostic features. Here, we comprehensively characterize the recently identified claudin-low tumor subtype.
Methods
The clinical, pathological and biological features of claudin-low tumors were compared to the other tumor subtypes using an updated human tumor database and multiple independent data sets. These main features of claudin-low tumors were also evaluated in a panel of breast cancer cell lines and genetically engineered mouse models.
Results
Claudin-low tumors are characterized by the low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features. Clinically, the majority of claudin-low tumors are poor prognosis estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Interestingly, we show that a group of highly utilized breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell.
Conclusions
These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines.
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