The prognostic role of loss of insulin-like growth factor-binding protein-3 expression in head and neck carcinogenesis.

The activities of insulin-like growth factors (IGFs) in regulating cell proliferation, differentiation, and apoptosis are modulated by a family of high-affinity specific IGF-binding proteins (IGFBPs), IGFBP-3 being the most abundant in circulation. Down-regulation of IGFBP-3 has been shown to be associated with a shorter disease-specific survival probability in early non-small-cell lung cancer (NSCLC). We examined the prognostic role of IGFBP-3 protein expression loss in 34 squamous cell carcinomas (SCC) of the tongue (stages II-IV) and 30 premalignant lesions of the oral cavity and the larynx. Reduced IGFBP-3 expression was found in 11 (32%) of 34 tongue SCC cases, and was associated with significantly shorter disease-specific and disease-free survival (P=0.0002 and <0.0001 by Log-rank test). In premalignant lesions, IGFBP3 loss was found in 8 (27%) of 30 cases without significant association with cancer-free survival. Therefore, down-regulation of IGFBP-3 is an early event during head and neck carcinogenesis, that bears an adverse prognostic significance in tongue cancer and could serve as both a marker of aggressive disease and target for intervention.