Furudoi A, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G, Shimamoto F
The First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.
Oncology. 2001;60(2):162-9. doi: 10.1159/000055314.
Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC).
One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells.
Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke's stage (Duke's <D, 32% vs. Duke's D, 51%). In the central portion and superficial part, there were no significant differences between Glut1, Ki-67 expression and clinicopathological findings. Glut1 expression at the deepest invasive site correlated significantly with the Ki-67 labeling index. In cases of curative surgery, patients with Glut1-positive lesions at the deepest invasive site showed a significantly poorer prognosis than those with Glut1-negative lesions. Multivariate analysis with logistic regression for 5-year survival in patients who had undergone curative surgery showed that lymph node metastasis and Glut1 expression were significant risk factors.
These results indicate that Glut1 expression at the deepest site of tumor invasion can be a useful predictor of a high malignant potential and poor prognosis in advanced CRC.
恶性细胞在体外和体内均表现出葡萄糖摄取和利用增加。这一过程被认为是由葡萄糖转运蛋白（Glut）家族介导的。本研究的目的是阐明在最深浸润部位的Glut1表达作为晚期结直肠癌（CRC）侵袭/转移潜能和预后预测指标的临床意义。
152例接受晚期CRC手术切除的患者纳入本研究。最深浸润部位的组织学亚分类包括高分化（W）、中高分化（Mw）、中低分化（Mp）、低分化（Por）和黏液腺癌（Muc）。使用抗Glut1多克隆抗体MYM，采用标记链霉亲和素-生物素试剂盒进行免疫组织化学检测Glut1表达。作为细胞增殖标志物，还检测了Ki-67表达。所有免疫反应性均在最深浸润部位、中央部分和浅表部分进行分析。如果在至少30%的肿瘤细胞中观察到膜或细胞质的明显染色，则将Glut1的免疫组织化学表达定义为阳性。
在152个病变的56个（36.8%）最深浸润部位检测到Glut1表达。最深浸润部位的Glut1表达发生率与组织学分级（W/Mw级，28%对Mp/Por/Muc级，48%）、浸润深度（固有肌层浸润/浆膜下或外膜下浸润，29%对浆膜或外膜浸润/邻近结构浸润，52%）、淋巴浸润（无淋巴浸润，19%对有淋巴浸润，40%）、淋巴结转移（无淋巴结转移，25%对有淋巴结转移，41%）和杜克分期（杜克分期<D，32%对杜克分期D，51%）显著相关。在中央部分和浅表部分，Glut1、Ki-67表达与临床病理结果之间无显著差异。最深浸润部位的Glut1表达与Ki-67标记指数显著相关。在根治性手术病例中，最深浸润部位Glut1阳性病变的患者预后明显比Glut1阴性病变的患者差。对接受根治性手术患者的5年生存率进行逻辑回归多因素分析显示，淋巴结转移和Glut1表达是显著的危险因素。
这些结果表明，肿瘤浸润最深部位的Glut1表达可作为晚期CRC高恶性潜能和不良预后的有用预测指标。
