血清p53抗体与食管癌化疗敏感性的关系

Correlation between Serum p53 Antibody and Chemosensitivity in Patient with Esophageal Cancer

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?

BACKGROUND & OBJECTIYE: Studies have revealed that overexpres si on of p53 protein has close relation to induction of drug resistance in caner pa tients 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 o f serum p53- Ab is closely correlated with p53 protein overexpression. Thus, se rum p53- Ab could theoretically be useful in predicting chemosensitivity in can cer patients. In the present study, we investigated whether preoperative serum p 53- Ab is correlated with the postoperative chemosensitivity of esophageal canc er, which was analyzed using in vitro drug response assay. METHOD: Serum analysi s of p53 antibodies was performed by enzyme- linked immuno- sorbent assay (EL ISA) in 38 patients with esophageal cancer preoperatively, then surgically resec ted specimens were analyzed for their chemosensitivity to cisdichlorodiamminepla tinum (DDP),5- fluorouracil (5- FU), and Adriamycin (ADM)by in vitro drug res ponse 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 pat ients was significantly different from that in healthy blood donors (P< 0.01). T he 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 sign ificant correlation between serum p53- Ab positive rate and TNM stage was obser ved (P< 0.05). The positive rate of serum p53- Ab were 21.5% (3/14), 50% (6/1 2), 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 po sitive serum p53- Ab was significantly lower than that of the patients with neg ative p53- Ab (60% , 45% , and 35% ; P< 0.01,P< 0.05, and P< 0.05, respectiv ely). CONCLUSION: p53- Ab is not only a prognostic marker for patients with eso phageal cancer, but also a predictor of their response to chemotherapy.