title: Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer.
abstract: Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250-300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time.
authors.affiliation: Department of Pathology, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Avilés-Salas
authors.affiliation: Experimental Oncology Laboratory, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: Saé
authors.initials: S
authors.lastname: Muñiz-Hernández
authors.affiliation: Department of Pathology, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: Héctor Aquiles
authors.initials: HA
authors.lastname: Maldonado-Martínez
authors.affiliation: Department of Pathology, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: José G
authors.initials: JG
authors.lastname: Chanona-Vilchis
authors.affiliation: Experimental Oncology Laboratory, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: Laura-Alejandra
authors.initials: LA
authors.lastname: Ramírez-Tirado
authors.affiliation: Experimental Oncology Laboratory, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: HernáNdez-Pedro
authors.affiliation: Department of Pathology, Medica Sur Clinic and Foundation, 14050 Mexico City, Mexico.
authors.forename: Rita
authors.initials: R
authors.lastname: Dorantes-Heredia
authors.affiliation: Oncology Center, Medica Sur Clinic and Foundation, 14050 Mexico City, Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: RuíZ-Morales
authors.affiliation: Oncology Center, Medica Sur Clinic and Foundation, 14050 Mexico City, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Motola-Kuba
authors.affiliation: Experimental Oncology Laboratory, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico; Thoracic Oncology Unit, National Cancer Institute of Mexico (INCan), 14080 Mexico City, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
keywords: H-score; biomarkers; cetuximab; epidermal growth factor receptor; immunohistochemistry; necitumumab; non-small cell lung cancer; tumor