EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target

• Published in: British journal of cancer 2011-07, Vol.105 (3), p.420-427
• Main Authors: Iida, K, Nakayama, K, Rahman, M T, Rahman, M, Ishikawa, M, Katagiri, A, Yeasmin, S, Otsuki, Y, Kobayashi, H, Nakayama, S, Miyazaki, K
• Format: Article
• Language: English
• Subjects: 631/67/1059/602; 692/420/2489/68; 692/699/67/1517/1371; Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenosquamous; Adolescent; Adult; Aged; Aged, 80 and over; Animal models; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Cell survival; Cervical cancer; Cervical carcinoma; Cervix; Child; Child, Preschool; Clinical outcomes; Data processing; Development; Drug Resistance; Epidemiology; Epidermal growth factor receptors; Exons; Female; Female genital diseases; Gene Amplification; Genes, erbB-1; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; K-Ras protein; Medical sciences; Mice; Mice, Nude; Middle Aged; Molecular Diagnostics; Molecular Medicine; Molecular Targeted Therapy; Multivariate analysis; Mutation; Oncology; Protein-tyrosine kinase; Quinazolines; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; squamous cell carcinoma; Tumors; Tyrphostins - pharmacology; Up-Regulation; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - mortality; Uterus; Xenografts
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.222

Background: The aim of this study was to investigate the patterns of epidermal growth factor receptor (EGFR) overexpression, EGFR gene amplification, and the presence of activating mutations in the tyrosine kinase domain of this gene in squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas of the uterine cervix. Methods: The EGFR expression, amplification, and mutation in cervical carcinomas were assessed by immunohistochemistry, fluorescence in situ hybridisation, and PCR–SSCP, respectively, and correlated with clinical data collected by a retrospective chart review. A functional assessment was performed by inactivating EGFR in cervical cancer cells with the potent inhibitor AG1478. Results: Immunohistochemical analysis revealed that 6 out of 59 (10.2%) cervical squamous cell carcinomas showed significant amplification of the EGFR locus, whereas none of the 52 adeno/adenosquamous cell carcinomas had detectable EGFR amplification ( P