Browsing by Subject "Triple negative"

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    Microglandular adenosis: a non-obligate precursor of triple-negative breast cancer?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Wen, Yong Hannah; Weigelt, Britta; Reis-Filho, Jorge S.
    Microglandular adenosis is a rare glandular lesion of the breast, which can mimic well-differentiated invasive carcinoma, and is characterized by a haphazard proliferation of uniform small round glands with open lumina and lacking a myoepithelial cell layer. This lesion has a rather unique immunohistochemical profile characterized by expression of cytokeratins and S-100, and lack of estrogen receptor (ER) and progesterone receptor (PR). The role of microglandular adenosis as a potential precursor of invasive breast cancer has long been a matter of controversy; however, recent molecular analyses have demonstrated that these lesions are heterogeneous at the genetic level, and that at least a subset of microglandular adenosis are clonal and display gene copy number alterations. Importantly, the pattern of genetic aberrations found in microglandular adenosis differs from that of other non-obligate precursors of ER-positive breast cancer. Carcinomas arising in microglandular adenosis are mostly of triple-negative phenotype (i.e. lack of ER, PR and HER2) and express S100, similar to microglandular adenosis. Genetic alterations found in microglandular adenosis have been shown to be similar to those found in synchronous invasive carcinomas. Here we review the clinical, morphological, and molecular features of microglandular adenosis, with an emphasis on its role as a non-obligate precursor of triple-negative breast cancer, and discuss areas for future research endeavors to clarify the clinical and biological significance of these fascinating lesions.
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    Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features
    (F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Martin, Vittoria; Botta, Francesca; Zanellato, Elena; Molinari, Francesca; Crippa, Stefano; Mazzucchelli, Luca; Frattini, Milo
    Aims: Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information. Methods and results: Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway. Conclusions: These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.