Bhatavdekar J M, Patel D D, Ghosh N, Chikhlikar P R, Trivedi T I, Suthar T P, Doctor S S, Shah N G, Balar D B
The Gujarat Cancer Society, Asarwa, Ahmedabad, India.
Dis Colon Rectum. 1997 Jul;40(7):785-90. doi: 10.1007/BF02055433.
This study was undertaken to evaluate the clinical use of Bcl-2, c-Myc, and p53 oncoproteins, either singly or in combination, as prognostic discriminants relative to recurrence and overall survival in patients with Dukes B or C colorectal carcinoma.
Analyses were made on archival pathology tissues of 48 patients with colorectal cancer. The oncoproteins were localized using commercially available monoclonal antibodies: clone 124 for Bcl-2, 9E11 for c-Myc, and DO-7 for p53. The avidin-biotin peroxidase complex method was used. Patients were followed up for a period of 2 to 36 months.
Expression of Bcl-2 and c-Myc was cytoplasmic, whereas nuclear p53 immunoreactivity was localized in the tumor cells. Sixty percent (29/48), 65 percent (31/48), and 37 percent (18/48) of the tumors showed overexpression of Bcl-2, c-Myc, and p53 oncoproteins, respectively. Fifty-four percent (18/33) and 100 percent (9/9) of moderately and poorly differentiated tumors, respectively, were positive for Bcl-2 (P < 0.01). No such correlation was noted for c-Myc and p53 oncoproteins. Univariate analysis showed that patients with Bcl-2 and c-Myc overexpression were associated with poorer overall survival than patients with Bcl-2-negative (P < 0.0124) and c-Myc-negative (P < 0.036) tumors. In addition, when patients were subgrouped according to Dukes stage, a statistically significant poorer overall survival was observed in Dukes C patients with Bcl-2-positive tumors (P < 0.017). Furthermore, multivariate analysis revealed that coexpression of three oncoproteins was predictive of a worse prognosis than for those individuals expressing none of the oncoproteins (P < 0.031) and only one positive oncoprotein (P < 0.014).
These findings suggest that oncoprotein coexpression possesses significant prognostic and potential therapeutic value; incorporation of molecular markers into future prospective randomized trials is advisable.
本研究旨在评估Bcl-2、c-Myc和p53癌蛋白单独或联合作为Dukes B或C期结直肠癌患者复发和总生存预后判别指标的临床应用价值。
对48例结直肠癌患者的存档病理组织进行分析。使用市售单克隆抗体定位癌蛋白：用于Bcl-2的克隆124、用于c-Myc的9E11和用于p53的DO-7。采用抗生物素蛋白-生物素过氧化物酶复合物法。对患者进行了2至36个月的随访。
Bcl-2和c-Myc的表达位于细胞质，而核p53免疫反应性定位于肿瘤细胞。分别有60%（29/48）、65%（31/48）和37%（18/48）的肿瘤显示Bcl-2、c-Myc和p53癌蛋白过表达。中分化和低分化肿瘤分别有54%（18/33）和100%（9/9）的Bcl-2呈阳性（P<0.01）。未发现c-Myc和p53癌蛋白有此类相关性。单因素分析显示，Bcl-2和c-Myc过表达的患者总生存较Bcl-2阴性（P<0.0124）和c-Myc阴性（P<0.036）的患者差。此外，根据Dukes分期对患者进行亚组分析时，Dukes C期Bcl-2阳性肿瘤患者的总生存显著较差（P<0.017）。此外，多因素分析显示，三种癌蛋白的共表达比不表达任何癌蛋白（P<0.031）和仅一种癌蛋白呈阳性（P<0.014）的患者预后更差。
这些发现表明癌蛋白共表达具有显著的预后和潜在治疗价值；建议将分子标志物纳入未来的前瞻性随机试验。
