Premium
Prostacyclin‐synthase expression in head and neck carcinoma patients and its prognostic value in the response to radiotherapy
Author(s) -
Camacho Mercedes,
Piñeiro Zenaida,
Alcolea Sonia,
García Jacinto,
Balart Josep,
Terra Ximena,
AvilésJurado FrancescXavier,
Soler Marta,
Quer Miquel,
León Xavier,
Vila Luis
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4453
Subject(s) - head and neck squamous cell carcinoma , radiation therapy , prostacyclin , medicine , chemoradiotherapy , cancer research , angiogenesis , cancer , oncology , head and neck cancer
Prostacyclin ( PGI 2 ) plays a role in cancer progression but the mechanism is currently poorly understood. Additionally, no data are available about the prognostic value of the PGI 2 pathway in head and neck squamous cell carcinoma ( HNSCC ) therapy. We evaluated the expression of the PGI 2 pathway in HNSCC patients. PGI 2 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 PGI 2 . However, HNSCC ‐conditioned media enhanced PGI 2 production in endothelial cells ( ECs ). The stable analogue of PGI 2 , carbaprostacyclin ( cPGI 2 ), exerted little effect on HNSCC cell line migration, and no effect on cell cycle distribution or proliferation rate after radiation injury was observed. Nevertheless, cPGI 2 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 PGI 2 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. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.