Koukourakis M I, Giatromanolaki A, Sivridis E, Simopoulos K, Pissakas G, Gatter K C, Harris A L
Tumour and Angiogenesis Research Group, Department of Radiotherapy-Oncology, Democritus University of Thrace, Alexandroupolis, Greece.
Anticancer Res. 2001 Nov-Dec;21(6B):4301-9.
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-induced changes in the microvessel density (MVD) and in the expression of the angiogenic factor thymidine phosphorylase (TP) in SCHNC.
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.
The irradiated samples were composed of cancer cell islets or bands, immersed within avascular degenerated tissue. In tumours that did 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).
The present study supports the idea that intensified angiogenic growth (angiogenic regeneration) during radiotherapy is associated with failure of radiotherapy.
肿瘤内新生血管形成是肿瘤进展的关键过程。尽管少数实验研究报道了细胞毒性治疗期间血管生成途径的强化，但血管生成在放疗反应中的作用尚不清楚。我们最近报道了强烈的血管生成对头颈部鳞状细胞癌（SCHNC）放疗结果的不利影响。在本研究中，我们调查了SCHNC放疗诱导的微血管密度（MVD）变化以及血管生成因子胸苷磷酸化酶（TP）的表达变化。
24例SCHNC患者在接受20Gy常规分割放疗前后立即对原发灶进行活检。采用免疫组化法评估MVD和TP的表达。
照射后的样本由癌细胞岛或条索组成，浸润于无血管的变性组织中。在放疗结束后未达到完全缓解的肿瘤中，这些存活的癌组织区域的MVD显著更高（p = 0.006），且核TP表达的癌细胞百分比增加（p = 0.0004），高于放疗前标本中的MVD和TP表达。这些癌岛中的TP表达与MVD直接相关（p = 0.004，r = 0.56）。
本研究支持放疗期间血管生成生长增强（血管生成再生）与放疗失败相关的观点。
