Lechpammer Mirna, Lukac Josip, Lechpammer Stanislav, Kovacević Dujo, Loda Massimo, Kusić Zvonko
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Int J Colorectal Dis. 2004 Mar;19(2):114-20. doi: 10.1007/s00384-003-0553-5. Epub 2003 Nov 21.
Overexpression of p53 protein in malignancies induces an immune response in some cancer patients. We investigated whether production of serum antibodies against p53 (p53-Ab) is associated with pathohistological parameters of colorectal carcinoma and whether p53-Ab can serve as a tumor marker during cancer treatment.
Serum samples from 220 colorectal cancer patients during surgery and adjuvant chemotherapy and 42 healthy controls were tested for the presence of p53-Ab by ELISA. Expression of p53 protein in tumors was determined using mouse anti-human p53-Ab.
Serum p53-Ab were detected in 18% of patients while all controls were negative. A strong correlation between p53-Ab production and p53 protein expression was observed: 70% of p53-Ab positive cases had tumors positive for p53 vs. 52% of p53-Ab negative cases. There was also a significant predominance of p53-Ab positive cases in Dukes' stages B and C over stage A. Although surgery alone reduced p53-Ab levels, decreases in p53-Ab titer became significant midterm through chemotherapy compared to both pre- and postoperative values and remained decreased until the completion of treatment.
The presence of p53-Ab in sera of patients with colorectal cancer indicates tumors in more advanced histopathologic stages (Dukes' B, C). Due to low sensitivity (18%) p53-Ab are not recommendable as a preoperative marker for colorectal cancer. However, due to high specificity (100%), their monitoring after surgery and adjuvant chemotherapy has potential for early diagnosis of tumor relapse in p53-Ab positive cases.
恶性肿瘤中p53蛋白的过表达在一些癌症患者中可诱导免疫反应。我们研究了血清中抗p53抗体(p53-Ab)的产生是否与结肠直肠癌的病理组织学参数相关,以及p53-Ab在癌症治疗期间能否作为一种肿瘤标志物。
采用酶联免疫吸附测定法(ELISA)检测220例接受手术及辅助化疗的结肠直肠癌患者以及42例健康对照者血清中p53-Ab的存在情况。使用小鼠抗人p53-Ab测定肿瘤中p53蛋白的表达。
18%的患者血清中检测到p53-Ab,而所有对照者均为阴性。观察到p53-Ab产生与p53蛋白表达之间存在强相关性:p53-Ab阳性病例中有70%的肿瘤p53呈阳性,而p53-Ab阴性病例中这一比例为52%。在Dukes分期B和C期的p53-Ab阳性病例也显著多于A期。尽管单纯手术可降低p53-Ab水平,但与术前和术后值相比,化疗中期p53-Ab滴度的下降变得显著,并在治疗完成前一直保持下降。
结肠直肠癌患者血清中存在p53-Ab表明肿瘤处于更晚期的组织病理学阶段(Dukes B、C期)。由于敏感性较低(18%),p53-Ab不推荐作为结肠直肠癌的术前标志物。然而,由于特异性较高(100%),术后及辅助化疗后监测p53-Ab对于p53-Ab阳性病例肿瘤复发的早期诊断具有潜力。