Prognostic role of epiregulin/amphiregulin expression in recurrent/metastatic head and neck cancer treated with cetuximab

Yasunao Kogashiwa; Hitoshi Inoue; Kiyomi Kuba; Ryuichiro Araki; Masanori Yasuda; Mitsuhiko Nakahira; Masashi Sugasawa

doi:10.1002/hed.25353

Prognostic role of epiregulin/amphiregulin expression in recurrent/metastatic head and neck cancer treated with cetuximab

Head Neck. 2018 Nov;40(11):2424-2431. doi: 10.1002/hed.25353. Epub 2018 Oct 10.

Authors

Yasunao Kogashiwa¹, Hitoshi Inoue¹, Kiyomi Kuba¹, Ryuichiro Araki², Masanori Yasuda³, Mitsuhiko Nakahira¹, Masashi Sugasawa¹

Affiliations

¹ Department of Head and Neck Surgery, Otolaryngology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
² Community Health Science Center, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan.
³ Department of Pathology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.

PMID: 30302873
DOI: 10.1002/hed.25353

Abstract

Background: Cetuximab combined with chemoradiotherapy chemotherapy is the standard therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, survival benefit is limited. The purpose of this study was to investigate the expression of epiregulin (EREG) and amphiregulin (AREG), as predictive prognostic markers for the efficacy of cetuximab combined with chemotherapy in R/M HNSCC.

Methods: We conducted a retrospective analysis of 37 patients diagnosed with R/M HNSCC. Tumor samples were analyzed for EREG and AREG mRNA gene expression, and clinical outcomes evaluated.

Results: Values of EREG and AREG were associated with significantly longer overall survival (OS) (P = .03 and P = .01, respectively), as well as progression-free survival (PFS) (P = .04 and P = .04, respectively). Multivariate analysis revealed that AREG expression was significantly associated with OS and PFS.

Conclusions: Patients with recurrent/metastatic HNSCC with higher EREG and AREG gene expression appear to benefit more from cetuximab combined with chemoradiotherapy chemotherapy than those with lower expression.

Keywords: AREG; EREG; EGFR; biomarker; cetuximab.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Amphiregulin / genetics*
Analysis of Variance
Biomarkers, Tumor / analysis
Cetuximab / therapeutic use*
Chemoradiotherapy / methods
Cohort Studies
Databases, Factual
Disease-Free Survival
Epiregulin / genetics*
Female
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms / drug therapy
Head and Neck Neoplasms / genetics*
Head and Neck Neoplasms / mortality
Head and Neck Neoplasms / pathology
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Neoplasm Metastasis
Neoplasm Recurrence, Local / drug therapy
Neoplasm Recurrence, Local / genetics*
Neoplasm Recurrence, Local / mortality
Neoplasm Recurrence, Local / pathology
Prognosis
Proportional Hazards Models
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck / drug therapy
Squamous Cell Carcinoma of Head and Neck / genetics*
Squamous Cell Carcinoma of Head and Neck / mortality
Squamous Cell Carcinoma of Head and Neck / pathology
Survival Analysis
Treatment Outcome

Substances

Amphiregulin
Biomarkers, Tumor
Epiregulin
Cetuximab