Prostacyclin-synthase expression in head and neck carcinoma patients and its prognostic value in the response to radiotherapy.

Prostacyclin (PGI2 ) plays a role in cancer progression but the mechanism is currently poorly understood. Additionally, no data are available about the prognostic value of the PGI2 pathway in head and neck squamous cell carcinoma (HNSCC) therapy. We evaluated the expression of the PGI2 pathway in HNSCC patients. PGI2 production and PGI synthase (PGIS) expression, in terms of mRNA (RT-PCR) and protein (immunoblotting), were lower in tumour samples than in non-tumoural mucosa, whereas, as expected, COX-2 expression was increased in HNSCC tumour samples. Using local control of the tumour after radiotherapy or chemoradiotherapy as a dependent variable, patients were classified into two categories of PGIS transcript levels. The high-PGIS group had a significantly lower frequency of local and distant failure than the low-PGIS group, and the 5-year cancer-specific survival was higher [90.2% (95% CI 81.0-99.4%) versus 60.5% (95% CI 44.4-76.6%)]. None of the four HNSCC cell lines analysed expressed PGIS and therefore they did not produce PGI2 . However, HNSCC-conditioned media enhanced PGI2 production in endothelial cells (ECs). The stable analogue of PGI2 , carbaprostacyclin (cPGI2 ), exerted little effect on HNSCC cell line migration, and no effect on cell cycle distribution or proliferation rate after radiation injury was observed. Nevertheless, cPGI2 promoted EP-4-dependent in vitro angiogenesis. Von Willebrand factor expression (EC marker) and capillary density were significantly higher in the group of patients with high expression of PGIS. Our results indicate that PGIS expression was associated with radiotherapy efficiency. Although we do not provide direct evidence of a relationship between tumour vascularization and radiotherapy efficiency, our results suggest that the effect of PGI2 is related to its ability to promote vascularization. These results also support the concept that co-adjuvant therapy with PGIS enhancers, such as retinoids, could have therapeutic value for HNSCC treatment.

External validation of a risk group defined by recursive partitioning analysis in patients with head and neck carcinoma treated with surgery and postoperative radiotherapy.

BACKGROUND: Several clinical trials have proved that concurrent chemoradiotherapy is more efficacious than radiotherapy alone among high-risk patients with head and neck squamous cell carcinoma (HNSCC) who undergo surgery. A risk-group classification defined according to a recursive partitioning analysis (RPA) for these patients has been recently proposed. The objective of the present study was to carry out an external validation of this RPA-derived classification system. METHODS: A retrospective study of 442 HNSCC patients treated with surgery and postoperative radiotherapy was conducted. The external validity of the RPA-derived classification system was assessed, and its ability to stage patients and to predict locoregional control of the disease was compared with the TNM system. RESULTS: The RPA-derived classification system succeeded in obtaining a monotonic prognosis gradient in locoregional control of the disease with increasing stage, and achieved greater differences in survival between stages than the TNM and pTNM classifications. Besides, the RPA method had a better homogeneity of the categories included in each stage, and in the heterogeneity between stages. CONCLUSIONS: The RPA-derived classification system allowed for the clear definition of prognostic groups in surgically treated HNSCC patients, improving the prognostic capacity of the TNM and pTNM classifications. The RPA-derived classification system is a useful tool in the definition of patients who, given a poor prognosis, should be considered candidates to adjuvant chemoradiotherapy.