RESUMEN
Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.
Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Neoplasias de Cabeza y Cuello/mortalidad , Infecciones por Papillomavirus/complicaciones , Receptor IGF Tipo 1/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Transformación Celular Neoplásica/genética , Terapia Combinada , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Papillomaviridae , Carcinoma de Células Escamosas de Cabeza y Cuello , Adulto JovenRESUMEN
BACKGROUND: Alternative splicing of the vascular endothelial growth factor (VEGF) gene results in a family of antiangiogenic isoforms (VEGFxxx b), not yet investigated in squamous cell carcinoma of the head and neck (SCCHN). We examined, therefore, the prognostic value of the relative expression of VEGF isoforms in SCCHN. METHODS: A tissue microarray comprising 187 SCCHNs was studied by immunohistochemistry with total VEGF (panVEGF) and VEGFxxx b-specific antibodies, and scored by 2 assessors for intensity and proportion. Scores were combined and expression ratios calculated. RESULTS: No meaningful significant differences were observed between panVEGF, VEGFxxx b, or expression ratio, and presence of lymphatic metastasis, or overall survival. This held true when tumor subsites were analyzed independently and when human papillomavirus (HPV) was accounted for in the oropharyngeal subgroup. CONCLUSION: Differential VEGF isoform expression is not a reliable prognostic biomarker for either the clinically node negative/pathologically node-positive neck or overall survival in pharyngeal and laryngeal SCCHNs.