Tsuboi Kaori, Asao Takayuki, Ide Munenori, Hashimoto Shinji, Noguchi Kasumi, Kominato Yoshihiko, Saniabadi Abby R, Kuwano Hiroyuki, Yazawa Shin
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan.
Ann Surg Oncol. 2007 Jun;14(6):1880-9. doi: 10.1245/s10434-007-9363-2. Epub 2007 Mar 21.
We have previously demonstrated tumor-specific alpha1,2fucosylation, which is associated with resistance of tumor cells to anticancer treatment in human colorectal tumor tissues. By using the YB-2 monoclonal antibody, the resulting products have been identified as Y, Le(b), and H type 2 antigens in colorectal tumor tissues.
Immunohistochemical analyses of colorectal cancer tissues (74 specimens) were performed with a newly established mouse monoclonal antibody, YB-3 specifically recognizing H disaccharide (Fucalpha1,2Galbeta) structures, and anti-A, anti-B, YB-2, and anti-sialyl Lewis X (SLX) antibodies, together with the analyses of glycosyltransferases involved in the synthesis of ABH antigens in the same tissues.
The YB-3 antibody enabled us to detect colorectal tumors, particularly tumors in the distal large intestine and the rectum, with high sensitivity (74.3%) and specificity (100%). From immunohistochemical and enzymatic analyses of colorectal tissues, we found that once alpha1,2fucosylation had proceeded in tumor tissues, blood group A or B antigen was also synthesized in approximately half of the tissues of A or B blood type, but not in their normal tissues. A correlation of survival rate with immunostaining of tissues was found only by YB-3 antibody and not by anti-A, anti-B, or anti-SLX antibody.
As a predictor of postoperative prognosis of patients with colorectal cancer, immunodetection of alpha1,2fucosylated antigens with the YB-3 antibody seemed to be superior to blood groups A, B, or SLX antigen in colorectal tumor tissues.
我们之前已经证明肿瘤特异性α1,2岩藻糖基化与人类结直肠肿瘤组织中肿瘤细胞对抗癌治疗的抗性相关。通过使用YB - 2单克隆抗体,在结直肠肿瘤组织中鉴定出的产物为Y、Le(b)和2型H抗原。
使用新建立的特异性识别H二糖(Fucα1,2Galβ)结构的小鼠单克隆抗体YB - 3以及抗A、抗B、YB - 2和抗唾液酸化Lewis X(SLX)抗体,对74例结直肠癌组织标本进行免疫组织化学分析,并对同一组织中ABH抗原合成所涉及的糖基转移酶进行分析。
YB - 3抗体使我们能够以高灵敏度(74.3%)和特异性(100%)检测结直肠肿瘤,特别是远端大肠和直肠中的肿瘤。通过对结直肠组织的免疫组织化学和酶分析,我们发现一旦肿瘤组织中发生了α1,2岩藻糖基化,大约一半的A型或B型血组织中也会合成A或B血型抗原,但在其正常组织中则不会。仅通过YB - 3抗体发现组织免疫染色与生存率之间存在相关性,而抗A、抗B或抗SLX抗体则未发现。
作为结直肠癌患者术后预后的预测指标,用YB - 3抗体免疫检测α1,2岩藻糖基化抗原在结直肠肿瘤组织中似乎优于A、B血型或SLX抗原。