Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Abstract

This study aimed to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of human papillomavirus (HPV) status, prognosis and potential relevance for targeted therapy. The protein expression of human epidermal growth factor receptor (Her)1–4 and c-Met were retrospectively assessed using semiquantitative immunohistochemistry on tissue microarrays and analyzed for correlations as well as differences in the clinicopathological criteria. Her1–4 and c-met were overexpressed compared to normal mucosa in 46%, 4%, 17%, 27% and 23%, respectively. Interestingly, most receptors were coexpressed. Her1 and c-Met were inversely correlated with p16 (p = 0.04; p = 0.02). Her2 and c-Met were associated with high tobacco consumption (p = 0.016; p = 0.04). High EGFR, Her3, Her4 and c-Met expression were associated with worse overall and disease-free survival (p ≤ 0.05). Furthermore, EGFR and c-Met expression showed raised hazard ratios of 2.53 (p = 0.02; 95% CI 1.24–5.18) and 2.45 (p = 0.02; 95% CI 1.13–5.35), respectively. Her4 was expressed less in distant metastases than in corresponding primary tumors and was correlated to a higher T category. EGFR and c-Met are relevant negative prognostic factors in OPSCC, independent of known clinicopathological parameters. We suggest dual targeting of EGFR and c-Met as a promising strategy for OPSCC treatment.

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

“…Previous studies aimed to identify gene signatures for HNSCC, allowing predicting patients' therapy responses, pathobiology, and survival. However, the suggested signatures still failed to be used in the clinical routine to guide (targeted therapy) treatments for all patients [11,12]. Alongside methodological complications, the fact that HNSCC is characterized by highly heterogeneous tumors and anatomical localizations makes the selection of relevant patient subpopulations difficult and prevents rapid progress.…”

Standardized Digital Image Analysis of PD-L1 Expression in Head and Neck Squamous Cell Carcinoma Reveals Intra- and Inter-Sample Heterogeneity with Therapeutic Implications

“…Two cores of human muscle tissue were placed in each recipient block to serve as a negative control and a reference for orientation. For later identification, samples’ positions were marked in a grid [ 15 ].…”

Prognostic stratification of oropharyngeal cancer patients in a betel nut chewing and low HPV area

“…S2B) [ 10 ]. The percentages of tumor cells with membranous EGFR staining were multiplied by the staining intensity score (1 + : weak; 2 + : intermediate; and 3 + : strong) to obtain the H-score for EGFR immunoreactivity, which ranges from 0 to 300 [ 6 , 7 ]. A H-score ≥ 200 was considered as high EGFR expression (Additional file 5 : Fig.…”

“…In addition to p16 status, several biomarkers such as epidermal growth factor receptor (EGFR), programmed cell death ligand 1 (PD-L1), and p53 have been investigated in OPC. Overexpression of EGFR has been reported to have negative prognostic impact in OPC [ 6 , 7 ]. P16-negative and EGFR-positive OPC have significantly poorer outcomes than p16-positive and EGFR-negative OPC [ 6 ].…”