Folate receptor alpha FRA expression in breast cancer: identification of a new molecular subtype and association with triple negative diseaseReportar como inadecuado

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MedicineBreast Cancer


Given that several targeted therapies directed towards folate receptor alpha FRA are in late stage clinical development, the sensitive and robust detection of FRA in tissues is of paramount importance relative to patient selection, prognosis and prediction. In the present study we undertook an immunohistochemical evaluation of expression of FRA in breast cancer samples using formalin-fixed, paraffin-embedded FFPE tissues, primarily invasive ductal carcinomas, using a newly described monoclonal antibody, 26B3. Samples assessed included both tissue microarrays TMA and whole tissue sections from archival tissue blocks. Normal breast shows a highly restricted expression of FRA to luminal membrane staining of secretory ductal cells, consistent with FRA secretion into milk. In early stage stages I-III invasive ductal carcinomas, FRA staining was observed in approximately 30% of all samples, independent of molecular subtype estrogen receptor ER-progesterone receptor PR-human epidermal growth factor receptor type 2 Her2. However, FRA expression was shown to associate with ER-PR negative tumors relative to ER-PR positive tumors p = 0.012 and perhaps more importantly, with triple negative breast cancers TNBC; p < 0.0001. FRA immunoreactivity was also shown to be retained in stage IV metastatic breast cancer samples from diverse anatomic sites including lymph node and bone. In metastatic breast cancer, FRA was shown to be expressed in 86% of TNBC patients. Taken together, these data suggest that FRA expressing breast cancer represents a novel molecular subtype and, further, may represent a new therapeutic target for this devastating disease.

KeywordsFolate receptor alpha FRA Breast cancer Triple negative breast cancer Immunohistochemistry IHC AbbreviationsFRAFolate receptor alpha, folate receptor α

FRBFolate receptor beta, folate receptor β

FRGFolate receptor gamma, folate receptor γ

FRDFolate receptor delta, folate receptor δ


MAbMonoclonal antibody

FFPEFormalin-fixed, paraffin-embedded

FNAFine needle aspirate

TMATissue microarray

IDCInvasive ductal carcinoma

DCISDuctal carcinoma in situ

EREstrogen receptor

PRProgesterone receptor

Her2Human epidermal growth factor receptor type 2

TNBCTriple negative breast cancer

TNMTumor node metastasis.

Electronic supplementary materialThe online version of this article doi:10.1186-2193-1801-1-22 contains supplementary material, which is available to authorized users.

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Autor: Daniel J O’Shannessy - Elizabeth B Somers - Julia Maltzman - Robert Smale - Yao-Shi Fu


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