Lavieille J P, Righini C, Reyt E, Brambilla C, Riva C
Airways Cancer Research Group, Albert Bonniot Institute, La Tronche, France.
Oral Oncol. 1998 Mar;34(2):84-92. doi: 10.1016/s1368-8375(97)00054-7.
Point mutations at the tumour suppressor gene p53 are one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN), which lead to the nuclear accumulation and overexpression of inactive p53 protein. The overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. p53 protein was studied in 112 SCCHN. Biopsies and sera samples were collected before initiation of treatment. 74 patients received neoadjuvant chemotherapy (5-fluorouracil-cisplatin-folinic acid). p53 protein expression was evaluated by immunohistochemistry (IHC) on paraffin-embedded sections. The analysis of mutations was assessed by PCR-SSCP of exons 5-10 on DNA from 28 representative cases. Antibodies specific for p53 protein were analysed in sera of 74 patients by an ELISA procedure. Overexpression (> 20% positive cells) of p53 protein was frequent (56%: 63/112) and was correlated with localisation of the primary tumour and tumour stage. p53 mutations were detected in 57% (16/28) of studied cases. The prevalence of p53 antibodies in sera was high (44% 32/74) and among this population, 68% (20/29) had a positive immunophenotype and 67% (6/9) a p53 mutation in the tumour. In addition, the presence of anti-p53 antibodies was slightly associated with complete response to neoadjuvant chemotherapy. If the humoral response seems to be an indicator of the p53 protein status, the detection of anti-p53 antibodies could be a good approach in the early detection of the presence of p53 alterations in SCCHN and recurrent tumours or the appearance of second primary cancer.
肿瘤抑制基因p53的点突变是头颈部鳞状细胞癌（SCCHN）中最常见的基因改变之一，这会导致无活性p53蛋白在细胞核内积聚并过度表达。突变型p53蛋白的过度表达可在癌症患者中诱导特异性体液反应。对112例头颈部鳞状细胞癌患者的p53蛋白进行了研究。在治疗开始前采集活检组织和血清样本。74例患者接受了新辅助化疗（5-氟尿嘧啶-顺铂-亚叶酸）。通过免疫组织化学（IHC）对石蜡包埋切片评估p53蛋白表达。通过对28例代表性病例的DNA进行外显子5-10的PCR-SSCP评估突变情况。采用ELISA法分析74例患者血清中针对p53蛋白的特异性抗体。p53蛋白过度表达（>20%阳性细胞）很常见（56%：63/112），且与原发肿瘤的部位和肿瘤分期相关。在所研究的病例中，57%（16/28）检测到p53突变。血清中p53抗体的患病率很高（44%，32/74），在这一群体中，68%（20/29）具有阳性免疫表型，67%（6/9）肿瘤中有p53突变。此外，抗p53抗体的存在与新辅助化疗的完全缓解略有相关。如果体液反应似乎是p53蛋白状态的一个指标，那么检测抗p53抗体可能是早期检测头颈部鳞状细胞癌和复发性肿瘤中p53改变的存在或第二原发性癌症出现的一种好方法。
