Relationship between Epidermal Growth Factor Receptor Status, p16INK4A, and Outcome in Head and Neck Squamous Cell Carcinoma

Abstract

Background: Human papilloma virus (HPV) infection is a powerful prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). Increased epidermal growth factor receptor (EGFR) gene copy number and protein expression have been reported to be negative predictors of outcome. This study examined the relationship between HPV status, EGFR gene copy number, EGFR protein expression, and clinical outcome in HNSCC patients treated with chemoradiation. Methods: HPV status was determined using p16INK4A immunohistochemistry (IHC), EGFR gene copy number was evaluated with FISH, and EGFR protein expression by IHC in 212 subjects. Results: EGFR FISH was positive in 41 of 204 (20%) patients and was negatively correlated with failure-free survival (FFS; HR = 1.84, P = 0.027) and overall survival (OS; HR = 1.78, P = 0.082). For p16INK4A, 85 of 200 (42.5%) patients were found to be p16 positive, including 75 of 131 (57%) with oropharyngeal cancer. Patients with p16-positive oropharyngeal cancer had significantly improved FFS (HR = 0.28, P < 0.001) and OS (HR = 0.31, P = 0.002). Only 2 of 126 (1.6%) oropharyngeal cancer patients were found to be p16+/EGFR FISH+. EGFR IHC was positive in 81 of 93 (87%) of patients and was associated with poorer FFS (HR = 1.98, P = 0.35) and OS (HR = 2.52, P = 0.22). Conclusions: Increased EGFR gene copy number is largely restricted to p16INK4A-negative oropharyngeal cancer. Although p16INK4A and EGFR FISH are both predictive of outcome in univariate analyses, only p16INK4A remains independently predictive. Impact: Knowledge of HPV and EGFR status can have implications for treatment options and prognosis in HNSCC. Cancer Epidemiol Biomarkers Prev; 20(6); 1230–7. ©2011 AACR.

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

“…This may be attributable to higher EGFR copy number in HPV-negative compared with HPV-positive tumors [33][34][35][36]. EGFR signaling results in activation of several downstream pathways that may affect transcription or translation of VEGF, including the Ras/MAPK, PI3 K/ Akt/mTOR, and STAT3 pathways [37,38].…”

Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial

“…10,18,19 How HPV status aff ects the outlook of patients with recurrent or metastatic disease, or their response to treatment, is unknown. Some studies [20][21][22][23][24] have suggested interactions between HPV and the EGFR signalling pathway. Therefore, HPV status (as assessed by p16 immunohistochemistry of formalinfi xed paraffi n-embedded samples) might aff ect outcomes during anti-EGFR treatment.…”

The molecular characterisation of unusual subcutaneous spindle cell lesion of breast

“…EGFR immunopositive cells are indicated with brown chromogen within the cell membrane and cytoplasm. Three red signals ( EGFR gene; 7p12) and one green signal (Chromosome 7; 7p11.1-q11.1) indicate an increased EGFR to CEP7 ratio ( EGFR to CEP7 ratio ≥222 26). …”