Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/REF-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome
Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/REF-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome
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DOI：
10.1016/s0360-3016(00)01561-3
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发表时间：
2001-05-01
影响因子：
7
通讯作者：
Harris, AL
中科院分区：
文献类型：
--
作者：
Koukourakis, MI;Giatromanolaki, A;Harris, AL
目的：HAP 1/Ref-1核酸内切酶参与DNA链断裂的修复和多种转录因子的DNA结合激活。HAP 1也是野生型p53的有效激活剂，因此它在人类癌症对放疗和化疗的反应中具有多种可能的作用。应用免疫组织化学方法，对95例局部晚期头颈部鳞状细胞癌（HNC）根治性放疗后石蜡包埋组织中HAP 1和p53蛋白的表达进行了研究结果：HAP 1在正常上皮细胞和间质细胞核中均有表达。在癌细胞中经常观察到HAP 1核表达的缺失。具有高HAP 1核表达的肿瘤（阳性细胞%>平均值;平均值= 11%）分化良好（p = 0.06），并且经常出现晚期淋巴结疾病（p 0.01）。核HAP 1高表达与完全缓解率差（p = 0.00001）、局部无复发间隔较短（p < 0.0001）和生存率较差（p < 0.0008）显着相关，HAP 1核反应性与p53核积聚呈负相关（p = 0.003）。结论：HAP 1核表达与p53核积聚呈负相关，与放化疗抵抗和生存率低直接相关。需要进一步的临床研究来证实这些发现。(C)2001 Elsevier Science Inc.
Purpose: HAP1/Ref-1 endonuclease is involved in the repair of DNA strand breaks and in the activation of DNA binding of several transcription factors. HAP1 is also a potent activator of wild type p53, It therefore has multiple possible roles in the response of human cancer to radiotherapy and chemotherapy.Methods and Materials: The nuclear expression of HAP1 and p53 proteins was studied by immunohistochemistry in paraffin-embedded material from 95 patients with locally advanced squamous cell head-and-neck cancer (HNC) treated with radical radiotherapy (38 cases with induction platinum-based chemotherapy and 57 with concurrent platinum chemoradiotherapy),Results: HAP1 was present in the nuclei of normal epithelium and stromal cells. Loss of HAP1 nuclear expression was frequently noted in cancer cells. Tumors with high HAP1 nuclear expression (% of positive cells > mean; mean = 11%) were of good differentiation (p = 0.06) and presented frequently with advanced nodal disease (p 0.01). High nuclear HAP1 expression was significantly associated with poor complete response rate (p = 0.00001), shorter local relapse-free interval (p < 0.0001), and poorer survival (p < 0.0008), HAP1 nuclear reactivity was inversely associated with p53 nuclear accumulation (p = 0.003). The inverse correlation between HAP1 expression and prognosis was independent of p53 status.Conclusion: HAP1 nuclear expression in HNC is inversely associated with p53 nuclear accumulation and directly related to resistance to chemoradiotherapy and poor survival. Further clinical investigation is required to confirm these findings. (C) 2001 Elsevier Science Inc.