engleski

Nuclear EGFR in breast cancer - potential marker in optimization of EGFR targeted therapy?

AIM: Although EGFR targeted agents showed promising anti-tumor activity in patients, only 10-20% of them manifest major clinical response which suggests that criteria for patient selection are still suboptimal. Emerging evidences suggest existence of direct EGFR signaling pathway in breast cancer, involving transport of EGFR into the nucleus and transcriptional regulation of the target genes. Thus nuclear localization and action of EGFR constitutes additional mechanism of resistance to the EGFR targeted therapy. MATERIAL AND METHODS: Tissue microarrays (TMAs) were built from the cohort of 113 archival formalin fixed paraffin embedded invasive ductal carcinoma. Immunohistochemistry was performed for mEGFR and nEGFR with subsequent FISH analysis of EGFR gene status. RESULTS: mEGFR overexpression and EGFR gene amplification were detected in 2% cases while nEGFR was detected in 40% of cases, with 12% having high nEGFR staining. nEGFR correlated with tumor size (p= 0.0005), lymph node metastasis (p=0.0288), Nottingham prognostic index (p=0.0011) and estrogen receptor expression (p=0.0258). On univariate analysis nEGFR showed correlation with shorter overall survival in whole cohort as well in pre-menopausal group of patients. Multivariate analysis revealed nEGFR to be independent prognostic factor and showed 3.4 times greater mortality risk for high nEGFR expressing tumors comparing to nEGFR negative patients (hazard ration = 3.402 ; p=0.0026). CONCLUSION: These findings suggest that nEGFR might be a future marker in identifying breast cancer patients sensitive to EGFR inhibitors.

breast cancer; EGFR; nuclear EGFR; therapy

nije evidentirano