Hosch S B, Scheunemann P, Lüth M, Inndorf S, Stoecklein N H, Erbersdobler A, Rehders A, Gundlach M, Knoefel W T, Izbicki J R
Department of General Surgery, University of Hamburg, Hamburg, Germany.
J Gastrointest Surg. 2001 Nov-Dec;5(6):673-9. doi: 10.1016/s1091-255x(01)80111-6.
Despite radical surgery, the prognosis for colorectal cancer patients with liver metastases has not changed markedly. Furthermore, no standard adjuvant therapeutic regimen has been developed. Adjuvant therapy with monoclonal antibodies (e.g., against 17-1A), which has been shown to be effective in preventing metastatic relapse in patients with Dukes' C colorectal cancer, might be a promising approach for these patients. However, the cytotoxic effects of monoclonal antibodies can be blocked by coexpression of complement resistance factors that inhibit antibody-dependent complement-mediated cytotoxicity. We therefore analyzed immunohistochemically the expression of 17-1A and the membrane-bound complement resistance factors CD55 and CD59 on metastatic tumor cells in the livers of 71 patients with colorectal carcinoma who had undergone resection of their metastases with curative intent. In 67 (94%) of 71 patients, liver metastases with homogeneous expression of 17-1A was seen. Heterogeneous expression of 17-1A was seen in four patients (6%). Heterogeneous expression of CD55 or CD59 was observed in 8 (11%) of 71 patients and 4 (6%) of 71 patients, respectively. None of the patients showed homogeneous expression of either CD55 or CD59. All patients with CD55 or CD59 expression showed homogeneous 17-1A expression, whereas none of the four patients with heterogeneous 17-1A expression was positive for CD55 or CD59. Our data indicate that 17-1A is widely expressed on liver metastases of patients with colorectal carcinoma. Therefore patients with completely resected liver metastases might be suitable candidates for adjuvant therapy with and-17-1A antibody since only a few of these lesions showed coexpression of complement resistance factors.
尽管进行了根治性手术,但结直肠癌肝转移患者的预后并未显著改变。此外,尚未制定出标准的辅助治疗方案。单克隆抗体辅助治疗(例如,针对17-1A)已被证明可有效预防 Dukes' C 期结直肠癌患者的转移复发,可能是这些患者的一种有前景的治疗方法。然而,单克隆抗体的细胞毒性作用可被抑制抗体依赖性补体介导的细胞毒性的补体抗性因子的共表达所阻断。因此,我们采用免疫组织化学方法分析了71例接受了肝转移瘤根治性切除的结直肠癌患者肝脏转移瘤细胞上17-1A以及膜结合补体抗性因子CD55和CD59的表达情况。71例患者中有67例(94%)的肝转移灶呈现17-1A均匀表达。4例患者(6%)出现17-1A异质性表达。71例患者中有8例(11%)和4例(6%)分别观察到CD55或CD59的异质性表达。所有患者均未出现CD55或CD59的均匀表达。所有表达CD55或CD59的患者均呈现17-1A均匀表达,而4例17-1A异质性表达的患者中无一例CD55或CD59呈阳性。我们的数据表明,17-1A在结直肠癌患者的肝转移灶上广泛表达。因此,肝转移灶完全切除的患者可能是使用抗17-1A抗体进行辅助治疗的合适人选,因为只有少数这些病灶显示有补体抗性因子的共表达。