EGFR mutations in lung cancer. A morphological, immunohistochemical and molecular study of lung adenocarcinoma

Verdú Ma,b,∗, Trias Ia,b,c, Román Rb, Rodón Nb, Pubill Ca, Calvo Md, Garcia-Pelaez Bb, Diaz Ob, Puig Xa,b,c

a Histopat Laboratoris, Barcelona, Spain, b BIOPAT Biopatologia Molecular, Grup Assistencia, Barcelona, Spain, c Hospital de Barcelona, SCIAS, Grup Assistencia, Barcelona, Spain, d Universitat de Barcelona (UB), Departament d’Estadística, Barcelona, Spain



The study of epidermal growth factor receptor mutations has become essential for the treatment of lung cancer. The aim of this study was to find a correlation between morphological changes and EGFR mutational status using both immunohistochemistry and molecular techniques. We also analyzed the cross-reaction of the L858R mutation-specific monoclonal antibody in cases with HER2 amplification described previously in breast and gastric cancer.

A series of 100 primary lung adenocarcinomas were examined. Exon 19 E746 A750del and exon 21 L858R mutations were studied using immunohistochemistry with two specific monoclonal antibodies. Gene mutational status was determined using real-time PCR or Sanger sequencing followed by real-time PCR when negative.

EGFR mutations were detected in 22 cases (22%) by molecular techniques, being significantly more frequent in women, low grade carcinoma and lepidic subtype, (p-value <0.05 in all cases).

In addition, in our series presence of tumoral necrosis correlated with absence of mutations.

The anti-E746 A750del antibody achieved a 100% positive predictive value and a negative predictive value of 97.7% which could restrict the use of molecular techniques to the 7% of cases with an equivocal result. The antibody for L858R mutation showed inconsistent results compared to molecular techniques, giving false positive result in two adenocarcinomas with HER2 amplification. However, its negative predictive value was very high (98.9%).

The use of real-time PCR identifies mutations not detected by the other two techniques.

These new antibodies could be useful as a screening tool prior to EGFR molecular techniques.


Rev Esp Patol 2016;49(4):226-233