Retinoid X receptor overexpression desensitizes laryngeal epithelium to carcinogenic effects associated with epidermal growth factor receptor upregulation

摘要

Objective: Squamous cell carcinomas (SCCs) of the larynx are sequelae of hyperplastic and dysplastic lesions. Epidermal growth factor receptor (EGFR) is found frequently overexpressed in SCCs of the head and neck, although its regulatory role is not fully elucidated. Conversely, retinoid X receptor a (RXRα) mediates the reversing effects of retinoids on head and neck carcinogenesis. We examined the expression of EGFR in relation to the progress of laryngeal tumorigenesis and how this association is modulated by concurrent RXR presence. Design: A retrospective study. Setting: A basic research anatomy laboratory, operating within a tertiary care institution. Materials: Tissue samples from 129 patients with premalignant or malignant laryngeal lesions. Method: Paraffin-section immunohistochemistry. Main Outcome Measures: EGFR immunoreactivity in relation to histopathology progression, in both the presence and absence of RXR immunoexpression. Results: EGFR was upregulated along the epithelial deterioration toward neoplasia (p < .001) but was unaffected by tumour grade. In RXRα-positive cases, a markedly stronger induction of EGFR occurred with malignant transformation compared with the epithelia immunonegative for the nuclear receptor. Conclusion: This study suggests that RXRα confers to squamous cells a shielding effect against excessive mitogenic stimulation, which might be EGFR dependent. RXR-positive patients manifesting resistance to anti-EGFR agents could benefit from rexinoid administration.