血清 p53抗体与食管癌化疗敏感性的关系

背景与目的:近年许多资料报道 p53蛋白过表达与肿瘤耐药性的产生密切相关,可以作为预测肿瘤对化疗敏感性的指标.最近发现 p53蛋白过表达肿瘤患者血清中存在特异性的 p53抗体,且血清 p53抗体与 p53蛋白的过表达有着密切的关系,因而从理论上推测血清 p53抗体也可以作为预测肿瘤对化疗敏感性的指标.本研究通过体外药敏实验研究食管癌术后患者的肿瘤样本化疗敏感性和术前血清 p53抗体表达的关系.方法:采用 ELISA法检测 38例食管癌患者及 20例健康人血清 p53抗体的表达;采用 MTT比色法进行体外药物敏感实验,检测 38例食管癌患 者新鲜肿瘤组织标本对顺铂( DDP)、 5-氟尿嘧啶( 5-FU)、阿霉素( ADM)的敏感性.结果: 38例食管癌患者中血清 p53抗体阳性率为 47.3%( 18/38),与健康献血者 (0/20)比较有显著性差异 (P< 0.01).其中 TNM分期Ⅰ和Ⅱ期患者中血清 p53抗体阳性率为 25%( 5/20),Ⅲ和Ⅳ期为 72.2%( 13/18),表明血清 p53抗体阳性率与食管癌 TNM分期有关 (P< 0.05).细胞分化好、中等、差的患者血清 p53抗体阳性率分别为 21.5%( 3/14)、 50%( 6/12)、 75%( 9/12),显示血清 p53抗体阳性率与食管癌细胞分化程度有关 (P< 0.05).血清 p53抗体阳性患者对 DDP、 5-FU、 ADM敏感的比率( 11.1%、 16.7%、 5.6%)显著低于血清 p53抗体阴性患者( 60%、 45%、 45%; P值分别 < 0.01、 < 0.05、 < 0.05).结论:血清 p53抗体可以作为预测食管癌化疗敏感性的参考指标之一.

Correlation between serum p53 antibody and chemosensitivity in patient with esophageal cancer

BACKGROUND & OBJECTIVE: Studies have revealed that overexpression of p53 protein has close relation to induction of drug resistance in cancer patients and it can be used as a predictor for chemosensitivity of tumor. Recently, it has been found that specific p53 antibody (p53-Ab) presented in the serum of cancer patients with p53 protein overexpression. Furthermore, the presence of serum p53-Ab is closely correlated with p53 protein overexpression. Thus, serum p53-Ab could theoretically be useful in predicting chemosensitivity in cancer patients. In the present study, we investigated whether preoperative serum p53-Ab is correlated with the postoperative chemosensitivity of esophageal cancer, which was analyzed using in vitro drug response assay. METHOD: Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay (ELISA) in 38 patients with esophageal cancer preoperatively, then surgically resected specimens were analyzed for their chemosensitivity to cisdichlorodiammineplatinum (DDP),5-fluorouracil (5-FU), and Adriamycin (ADM) by in vitro drug response assay MTT colorimetry. RESULTS: Serum p53-Ab was present in 47.3% of the patients with esophageal cancer. The positive rate of serum p53-Abs in patients was significantly different from that in healthy blood donors (P< 0.01).The positive rate of serum p53-Ab was 25%(5/20) for the patients at stage I and II, and 72.2%(13/18) for the patients at stage III and IV.A significant correlation between serum p53-Ab positive rate and TNM stage was observed (P< 0.05).The positive rate of serum p53-Ab were 21.5%(3/14), 50%(6/12), 75% (9/12) for the patients with well, moderately,and poorly differentiated tumors, respectively. There was significant correlation between serum p53-Ab positive rate and tumor differentiation (P< 0.05). The chemosensitivity to DDP, 5-FU, and ADM (11.1%,16.1%,and 16.1%, respectively) of the patients with positive serum p53-Ab was significantly lower than that of the patients with negative p53-Ab (60%, 45%, and 35%; P< 0.01,P< 0.05, and P< 0.05, respectively). CONCLUSION: p53-Ab is not only a prognostic marker for patients with esophageal cancer, but also a predictor of their response to chemotherapy.