HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features

Vittoria Martin*, Francesca Botta*, Elena Zanellato, Francesca Molinari, Stefano Crippa, Luca Mazzucchelli and Milo Frattini

Institute of Pathology, Locarno, Switzerland
*These authors contributed equally to the work.

Offprint requests to: Dr. Vittoria Martin, Institute of Pathology, Via in Selva 24, 6600 Locarno, Switzerland. e-mail: vittoria.martin@ti.ch


Summary. 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
. Histol Histopathol 27, 785-792 (2012)

Key words: Triple negative, Breast cancers, Basal like features, EGFR-targeted therapy, PTEN, EGFR, Fluorescent in situ hybridization

DOI: 10.14670/HH-27.785