Squamous cell head and neck cancer: Evidence of angiogenic regeneration during radiotherapy
Koukourakis MI., Giatromanolaki A., Sivridis E., Simopoulos K., Pissakas G., Gatter KC., Harris AL.
Background and Purpose: Intra-tumoural neoangiogenesis is an essential process for tumour progression. Although intensification of angiogenic pathways during cytotoxic therapy has been reported by a few experimental studies, the role of angiogenesis in response to radiotherapy is unclear. We recently reported an adverse effect of intense angiogenesis in the radiotherapy outcome of squamous cell head and neck cancer (SCHNC). In the present study we investigated the radiotherapy-reduced changes in the microvessel density (MVD) and in the expression of the angiogenic factor thymidine phosphorylase (TP) in SCHNC, Patients and Methods: Twenty-four patients with SCHNC underwent a biopsy of the primary lesion immediately before and after delivery of 20Gy of conventionally fractionated radiotherapy. The MVD and the expression of TP was assessed with immunohistochemistry. Results: The irradiated samples were composed of cancer cell islets or bands, immersed within avascular degenerated tissue, In tumours that had not reach complete response after the end of radiotherapy, these viable cancer tissue areas had a significantly higher MVD P=0.006) and increased percentage of cancer cells with nuclear TP expression (p=0.0004) than the MVD and the TP expression noted in specimens before radiotherapy, TP expression in these islets was directly related to the MVD (p=0.004, r=0.56). Conclusion: The present study supports the idea that intensified angiogenic growth (angiogenic regeneration) during radiotherapy associated with failure of radiotherapy.