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.
Papadimitrakopoulou
Vassiliki A
VA
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. vpapadim@mdanderson.org
Brown
Erika N
EN
Liu
Diane D
DD
El-Naggar
Adel K
AK
Jack Lee
J
J
Hong
Waun Ki
WK
Lee
Ho-Young
HY
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology
D018972:Insulin-Like Growth Factor Binding Protein 3