title: EGFR expression and activation are common in HER2 positive and triple-negative breast tumours.
abstract: EGFR has been associated with unfavourable prognosis in patients with triple-negative breast carcinomas, although little is known about EGFR activation in these tumours. In a series of breast carcinomas (archived formalin fixed tumours, n=100), we investigated EGFR phosphorylation status at Tyr992 (pEGFR-Y992) and Tyr1068 (pEGFR-Y1068) by immunohistochemistry, along with EGFR protein expression (extracellular domain), gene amplification status (fluorescent in situ hybridization) and conventional clinicopathologic parameters. EGFR protein was present in 21.9%, while phosphorylation at Y1068 and Y992 was observed in 27.8% and 50.5% of tumours, respectively. None of the tumours showed EGFR gene amplification, whereas 21.1% exhibited chromosome 7 polysomy. The above EGFR parameters were usually not simultaneously detected and were not associated with each other. High grade (p=0.003), lymph node positive (p=0.045), estrogen receptor (ER) negative (p<0.001) tumours often expressed EGFR protein. EGFR-Y992 and Y1068 phosphorylation was inversely associated with ER presence (p=0.023 and p=0.029, respectively) but positively with HER2 expression status (p<0.001 and p=0.002, respectively). The global positivity for any EGFR parameter did not significantly differ between triple-negative and HER2 positive tumours. In conclusion, EGFR phosphorylation is commonly encountered in breast carcinomas, although unrelated to EGFR protein presence and gene amplification. EGFR may appear activated even in cases where the extracellular domain of this protein is not observed with immunohistochemistry. These findings may be useful for further studies aiming at the assessment of EGFR parameters on this type of material.
authors.affiliation: Department of Pathology, Aristotle University Medical School, Thessaloniki, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Koletsa
authors.forename: V
authors.initials: V
authors.lastname: Kotoula
authors.forename: G
authors.initials: G
authors.lastname: Karayannopoulou
authors.forename: E
authors.initials: E
authors.lastname: Nenopoulou
authors.forename: G
authors.initials: G
authors.lastname: Karkavelas
authors.forename: C S
authors.initials: CS
authors.lastname: Papadimitriou
authors.forename: I
authors.initials: I
authors.lastname: Kostopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human