Reis Henning, Tschirdewahn Stephan, Szarvas Tibor, Rübben Herbert, Schmid Kurt Werner, Grabellus Florian
Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Oncol Lett. 2011 Nov;2(6):1149-1153. doi: 10.3892/ol.2011.394. Epub 2011 Aug 29.
Glucose Transporter 1 (GLUT1) belongs to the expanding mammalian facilitative glucose transporter family. Elevated GLUT1 protein expression has been observed in the majority of urothelial carcinomas, with various effects on clinicopathological parameters. Whereas malignant cells have an accelerated metabolism with increased energy requirements, the membranous expression of GLUTs is amplified. GLUT1 protein expression was evaluated in urothelial tumours of increasing grade of malignancy, supplemented by a tumour proliferation analysis. Particular attention was paid to non-invasive precursors of urothelial carcinoma. A total of 105 paraffin-embedded samples were classified (normal urothelium, low/high-grade papillary carcinoma, carcinoma in situ and invasive carcinoma). Grading and staging were conducted using the 1998 ISUP/2004 WHO criteria. The staining intensity of GLUT1 was assessed with a standard immunoreactive score (IRS). The Ki-67 index was assessed by counting positive nuclei in representative urothelial hot spots. Results showed that an increased GLUT1-IRS and mean count of Ki-67-positive cells were significantly associated with an increased grade of malignancy (p<0.0001), particularly in non-invasive tumours. GLUT1-IRS was significantly associated with a Ki-67-labelled proliferative fraction (p<0.0001). No significant association regarding tumour grade or stage was observed within the invasive carcinoma group. GLUT1 protein expression was found to be strongly correlated with increased malignant potential, particularly in non-invasive urothelial carcinomas. The increase of GLUT1 expression may reflect a preinvasive metabolic switch in terms of enhanced cell metabolism concomitant to known genetic alterations. A further increase in invasive carcinomas may be related to hypoxic conditions.
葡萄糖转运蛋白1（GLUT1）属于不断扩大的哺乳动物易化性葡萄糖转运蛋白家族。在大多数尿路上皮癌中都观察到GLUT1蛋白表达升高，对临床病理参数有多种影响。恶性细胞具有加速的新陈代谢，能量需求增加，因此葡萄糖转运蛋白的膜表达会增强。我们评估了恶性程度不断增加的尿路上皮肿瘤中GLUT1蛋白的表达，并辅以肿瘤增殖分析。特别关注了尿路上皮癌的非侵袭性前体。总共对105个石蜡包埋样本进行了分类（正常尿路上皮、低/高级别乳头状癌、原位癌和浸润性癌）。分级和分期采用1998年国际泌尿病理学会/2004年世界卫生组织标准。使用标准免疫反应评分（IRS）评估GLUT1的染色强度。通过对代表性尿路上皮热点中的阳性细胞核进行计数来评估Ki-67指数。结果表明，GLUT1-IRS升高和Ki-67阳性细胞的平均计数与恶性程度增加显著相关（p<0.0001），尤其是在非侵袭性肿瘤中。GLUT1-IRS与Ki-67标记的增殖分数显著相关（p<0.0001）。在浸润性癌组中，未观察到与肿瘤分级或分期的显著相关性。发现GLUT1蛋白表达与恶性潜能增加密切相关，尤其是在非侵袭性尿路上皮癌中。GLUT1表达的增加可能反映了一种侵袭前的代谢转变，即伴随着已知的基因改变，细胞代谢增强。浸润性癌中进一步的增加可能与缺氧条件有关。
