Montse Verdu1,2, Natalia Rodon2, Ruth Roman2, Isabel Trias1,2,3, Carme Pubill1, Nuria Arraiza1, Begonya Martinez1, Beatriz Garcia-Pelaez2 and Xavier Puig1,2,3.
1Histopat laboratoris, Barcelona, Spain; 2BIOPAT. Biopatolodia Molecular, Grup Assistencia, Barcelona, Spain and 3Hospital de Barcelona, SCIAS, Grup Assistencia, Barcelona, Spain.
Background: The use of epidermal growth factor receptor (EGFR) mutation-specific antibodies is likely to get soon incorporated into clinical practice due to its proven correlation with the presence of EGFR mutation in lung adenocarcinoma, especially in cases with limited tumor material, or in situations where molecular genetic analysis is not readily available.
The use of these antibodies has also been suggested as an additional tool for distinguishing primary versus metastatic carcinomas in the lung. Incidental findings in our routine practice and a recently published paper reporting false positive breast carcinomas for EGFR L858R, made us think about the possible existence of a cross-reaction between HER2 and the EGFR L858R-specific antibody.
Aims of this study were to further analyze the existence of this cross-reaction and its frequency in the two common sources of metastatic tumors to lung, breast and gastric cancer; in which, in addition, HER2 expression is widely studied in relation to targeted therapies.
Design: The series consists of 55 primary tumors, 22 breast and 5 gastric carcinomas HER2 positive for overexpression and amplification, and 20 breast and 8 gastric carcinomas negative for both. EGFR mutations were studied by immunohistochemistry with two specific monoclonal antibodies (EGFR [E746_750del] clone 6B6 and EGFR L858R clone 43B2) in all cases, and confirmed using real-time PCR when positive.
Results: In our study 86% (19/22) of HER2 positive breast carcinomas and 100% (5/5) of HER2 positive gastric carcinomas showed EGFR L858R positive expression, and equivocal in 14% (3/22) of HER2 positive breast carcinomas, while no expression was found in none of the HER2 negative carcinomas. All cases were negative using the EGFR exon19 [E746_750del] antibody. Real-time PCR did not confirm the presence of the EGFR L858R mutation on neither of the 24 positives nor of the 3 equivocal cases by IHC.
Conclusion: EGFR L858R antibody gives false positive results in most of breast and gastric carcinomas with HER2 overexpression/amplification. The existence of this cross-reaction makes necessary verify any EGFR L858R positivity by molecular methods and discard the presence of HER2 overexpression/amplification in order to establish its clinical significance.