Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance

Abstract

Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an important role in tumour angiogenesis and to influence prognosis in many cancers. However its prognostic value in head and neck squamous cell carcinomas (HNSCCs) remains controversial. Therefore, we investigated the clinical relevance of VEGF-A expression in HNSCCs and analysed whether its expression was associated with PAIP2 protein levels, a VEGF-A mRNA-binding partner that strongly regulates VEGF-A expression in tissue culture. We determined the correlation of VEGF-A and PAIP2 protein levels, quantitatively evaluated in tumour tissue homogenates from 54 patients with HNSCC, to clinicopathological parameters. We showed that VEGF-A expression in HNSCC is correlated to the stage of tumour differentiation ( P =0.050) and is an independent prognostic factor for progression-free survival ( P =0.001) and overall survival ( P =0.0004). In a pharynx carcinoma cell line, we demonstrated by RNA interference that VEGF-A expression is closely controlled by PAIP2. Moreover, in human HNSCCs, VEGF-A expression is significantly correlated to PAIP2 protein levels ( P =0.0018). Nevertheless, PAIP2 expression is associated with neither clinicopathological factors nor patient's survival. Our data suggest that, in contrast to PAIP2 protein levels, which are unrelated to tumour prognosis, VEGF-A expression could serve as a prognostic marker in head and neck cancer and may be helpful for targeted therapies.

Molecular Genetics and Biology of Head and Neck Squamous Cell Carcinoma: Implications for Diagnosis, Prognosis and Treatment

“…Many studies have shown that VEGF-A, as well as VEGF-C, are upregulated in head and neck cancers, thus stimulating proliferation of vascular and lymphatic endothelial cells, and increasing vessel permeability (Thomas et al, 2005). The enhanced angiogenic activity could sustain growth of the primary tumour, potentiate dissemination and also support the establishment of micrometastases (Onesto et al, 2006). This is consistent with the strong association observed in different studies between VEGF-A expression and distant recurrence.…”

“…However, the status of VEGF-A remains unclear since other HNSCC retrospective studies have shown no correlation between VEGF-A expression and prognosis (Onesto et al, 2006;Thomas et al, 2005). These conflicting results may be due partly to the method of detection of VEGF-A expression (i.e.IHC), used in most of the previous reports, and which is a semiquantitative method.…”

“…This is consistent with the strong association observed in different studies between VEGF-A expression and distant recurrence. It was also demonstrated that VEGF-A protein levels are closely associated to overall survival (Onesto et al, 2006). Subsequently, multivariate analysis showed that VEGF- …”

“…IHC) as well as a quantitative method (i.e. ELISA), it is shown that VEGF-A expression is significantly associated with the tumour differentiation stage, poorly differentiated tumours expressing higher VEGF-A levels than highly differentiated tumours in head and neck carcinomas (Onesto et al, 2006;Thomas et al, 2005). In conclusion, markers related to tumour neovascularization can also predict the outcome in head and neck cancer patients.…”

Update on Molecular Diagnostic Tests in Head and Neck Cancer

“…Using ELISA to quantify VEGF levels, one study showed that VEGF expression is associated with poorly differentiated head and neck cancers, higher rates of disease recurrence, metastatic disease, and shorter progression free survival. 98 Other studies have used laser capture microdissection followed by RT-PCR to compare VEGF mRNA levels in HNSCC with normal mucosa. A greater than seven-fold increase was found in the cancer samples.…”