FABP7 and HMGCS2 Are Novel Protein Markers for Apocrine Differentiation Categorizing Apocrine Carcinoma of the Breast

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dc.contributor.authorGromov, Pavel
dc.contributor.authorEspinoza, Jaime A.
dc.contributor.authorTalman, Maj-Lis
dc.contributor.authorHonma, Naoko
dc.contributor.authorKroman, Niels
dc.contributor.authorWielenga, Vera Timmermans
dc.contributor.authorMoreira, Jose M. A.
dc.contributor.authorGromova, Irina
dc.date.accessioned2025-01-23T21:40:03Z
dc.date.available2025-01-23T21:40:03Z
dc.date.issued2014
dc.description.abstractApocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast apocrine differentiation spectrum from benign metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is strongly associated with apocrine differentiation; their expression is retained by most invasive apocrine carcinomas (IAC) showing positive immunoreactivity in 100% and 78% of apocrine carcinomas, respectively, as compared to non-apocrine tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was shown to be associated with more aggressive stages of apocrine carcinomas. In addition, when added to the panel of apocrine biomarkers previously reported by our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may represent a golden molecular standard for defining the apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/ Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)-identifies IACs with a greater sensitivity (79%) as compared with the steroidal profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed immunohistochemical analysis of breast apocrine lesions with a panel of antibodies against proteins which correspond to 10 genes selected from published transcriptomic signatures that currently characterize molecular apocrine subtype and shown that except for melanophilin that is overexpressed in benign apocrine lesions, these proteins were not specific for morphological apocrine differentiation in breast.
dc.fuente.origenWOS
dc.identifier.doi10.1371/journal.pone.0112024
dc.identifier.issn1932-6203
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0112024
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101614
dc.identifier.wosidWOS:000349144400047
dc.issue.numero11
dc.language.isoen
dc.revistaPlos one
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFABP7 and HMGCS2 Are Novel Protein Markers for Apocrine Differentiation Categorizing Apocrine Carcinoma of the Breast
dc.typeartículo
dc.volumen9
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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