Increased Expression of Nuclear Factor E2 P45-related Factor 2 (NRF2) in Head and Neck Squamous Cell Carcinomas

Background: Head and neck squamous cell carcinoma (HNSCC) continues to cause significant morbidity and mortality. Overexpression of specific phase II gene products may represent an important biomarker. One regulator of phase II gene expression is the transcription factor nuclear factor E2 p45-related factor 2 (Nrf2). Nrf2 expression was evaluated in HNSCC, to determine whether it might serve as a biomarker for early detection of disease.

Methods: A tissue microarray was constructed of 141 HNSCC biopsy cores from 47 HNSCCs. In addition, histologically normal squamous mucosa was obtained from 7 patients. Protein expression was evaluated by immunohistochemistry.

Results: Nrf2 expression was increased in 91.5% of tumors. Expression of thioredoxin, a Nrf2-reguated gene product, was elevated in 75% of tumors. Keap1, which regulates the rate of Nrf2 ubiquitination and degradation, was relatively overexpressed in HNSCC compared with normal mucosa.

Conclusions: Nrf2 expression may be a possible HNSCC candidate biomarker.