EGFR Protein Expression Relates with Tumor Histology, Methylation Status of EGFR and HPV16 E6 Viral Load in Oropharyngeal Carcinoma
- 1 September 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Head and Neck Pathology
- Vol. 15 (3), 743-756
- https://doi.org/10.1007/s12105-020-01261-w
Abstract
The epidermal growth factor receptor (EGFR) pathway is important in tumorigenesis of oropharyngeal carcinoma (OPC). However, the molecular mechanisms contributing to EGFR expression in OPC are not well-known. To detect relating factors and clinicopathological impact of EGFR protein expression in OPC, gene amplification/loss, point mutations including synonymous mutations, and promoter methylation of EGFR, and the viral genome load of human papillomavirus type 16 (HPV16)-E5, -E6, and -E7, after extracting HPV16-related OPCs with qPCR of HPV16-E6 and E7, were investigated in 74 OPC surgical cases, including 52 HPV-related (HPV-OPC) and 22 HPV-unrelated (nHPV-OPC). Immunohistochemical (IHC) data of EGFR expression (high, weak, and negative), validated by the qPCR of EGFR mRNA, were compared with molecular, viral, and clinicopathological data of patients. All nHPV-OPC cases were EGFR-IHC-high, whereas 21.2%, 65.4%, and 13.5% of HPV-OPC cases showed EGFR-IHC-high, -weak, -negative (p < 0.01), respectively. In HPV-OPC cases, EGFR-IHC-weak/negative status was related to promoter methylation of EGFR (p = 0.009), but not with gene amplification/loss or the point mutation of EGFR and was more often seen in HPV16-OPC cases (p = 0.049). Among HPV16-OPC cases, EGFR-IHC-weak/negative was related to high E6 expression. EGFR protein-loss was related to the tumor histology of non-keratinizing squamous cell carcinoma (SCC) (p = 0.035) but not with patient prognosis. In conclusion, decreased EGFR protein expression was more frequent in HPV-OPC than in nHPV-OPC and was related to EGFR methylation, infection of HPV16, and the viral genome load of HPV16-E6. Clinicopathologically, it was related to the tumor histology of non-keratinizing SCC.This publication has 46 references indexed in Scilit:
- Epidermal growth factor receptor (EGFR) gene promoter methylation and cetuximab treatment in colorectal cancer patientsBritish Journal of Cancer, 2011
- Human Papillomavirus and Survival of Patients with Oropharyngeal CancerThe New England Journal of Medicine, 2010
- Human papillomavirus oncoproteins: pathways to transformationNature Reviews Cancer, 2010
- Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus‐associated head and neck cancer based on a prospective clinical experienceCancer, 2010
- EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal CancerJournal of Clinical Oncology, 2008
- Somatic Mutations of EGFR Gene in Squamous Cell Carcinoma of the Head and NeckClinical Cancer Research, 2005
- The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical CarcinogenesisCancer Research and Treatment, 2005
- HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasivenessJournal of Medical Virology, 2002
- Quantitation of human papillomavirus 16 E6 and E7 DNA and RNA in residual material from ThinPrep Papanicolaou tests using real‐time polymerase chain reaction analysisCancer, 2002
- Mechanisms of cell transformation by papillomavirus E5 proteinsOncogene, 2001