Juhl B R
Department of Pathology, Herlev University Hospital, Copenhagen.
Dan Med Bull. 1994 Feb;41(1):1-11.
Patients presenting histologically identical non-invasive tumours of the urinary bladder suffer a variable unpredictable clinical course, making the identification of prognostic markers relevant in the clinical setting. Recent histochemical studies have demonstrated that changes in cell surface carbohydrates during malignant transformation involve the blood group antigens. These oligosaccharides, initially defined on erythrocytes, are widely distributed in human tissue including human urothelium. This study was conducted in order to evaluate the prognostic value of blood group antigen determination in superficial bladder cancer. The aims of the present study were: 1. To standardize the immunohistochemical staining technique for blood group antigens, 2. To investigate the pattern of blood group antigen expression in non-neoplastic urothelium, the genetic heterogeneity, 3. To examine changes in the blood group antigen expression in bladder cancer, and 4. to assess the prognostic value of blood group antigen expression in superficial bladder cancers of morphological similar appearance. The ABH, Lewis, and Thomsen-Friedenreich (T) blood group antigens were studied by means of the Tween 20-modified indirect immunoperoxidase staining technique. Serial dilutions of antibodies and lectins were applied on dewaxed routinely processed tissue sections of normal ureters and transitional cell tumours. The reciprocal value of the highest dilution of antibody and lectin still giving staining defined the endpoint titer and allowed semiquantitative estimation of antigen content. In non-neoplastic urothelium the ABH, Lewis and T blood group antigens were heterogeneously expressed, and the expression correlated to the Lewis blood type. This indicates 1) a genetic regulated synthesis of ABH and Lewis blood group antigens similar to that operating in saliva, other secretions, epithelia, and erythrocytes, 2) a possible linkage between ABH-, Lewis-, and T antigen systems, if steric hindrance can be excluded. Based on the above findings in non-neoplastic urothelium the deviation in tumours from normal blood group antigen expression was quantified on a scale from 0 (normal) to 3 (total loss) for each antigen system separately. All scores were related to histological stage and grade suggesting a parallelism between morphological dedifferentiation and the degree of abnormal blood group expression. In superficial low grade tumours only A and Lewis a scores were related to prognosis. This held only true for patients with tumours of normal or nearly normal A and Lewis a antigen expression (scores 0 and 1), who had a favorable course as regards invasive recurrence and/or papillomatosis within 5 years. Prediction of an unfavorable outcome was not possible. Only a small number of superficial tumours exhibited normal blood group antigen expression.(ABSTRACT TRUNCATED AT 400 WORDS)
组织学上呈现相同的膀胱非侵袭性肿瘤的患者,其临床病程变化不定且无法预测,这使得在临床环境中识别相关预后标志物变得至关重要。最近的组织化学研究表明,恶性转化过程中细胞表面碳水化合物的变化涉及血型抗原。这些最初在红细胞上定义的寡糖,广泛分布于包括人尿路上皮在内的人体组织中。本研究旨在评估血型抗原测定在浅表性膀胱癌中的预后价值。本研究的目的如下:1. 标准化血型抗原的免疫组织化学染色技术;2. 研究非肿瘤性尿路上皮中血型抗原的表达模式、基因异质性;3. 检查膀胱癌中血型抗原表达的变化;4. 评估形态学外观相似的浅表性膀胱癌中血型抗原表达的预后价值。采用吐温20改良间接免疫过氧化物酶染色技术研究ABH、Lewis和汤姆森 - 弗里登赖希(T)血型抗原。将抗体和凝集素的系列稀释液应用于正常输尿管和移行细胞肿瘤的常规脱蜡处理组织切片上。仍能产生染色的抗体和凝集素的最高稀释倍数的倒数定义为终点滴度,并允许对抗原含量进行半定量估计。在非肿瘤性尿路上皮中,ABH、Lewis和T血型抗原呈异质性表达,且表达与Lewis血型相关。这表明:1)ABH和Lewis血型抗原的合成受基因调控,类似于在唾液、其他分泌物、上皮和红细胞中起作用的调控方式;2)如果可以排除空间位阻,ABH、Lewis和T抗原系统之间可能存在联系。基于非肿瘤性尿路上皮的上述发现,对于每个抗原系统,分别以0(正常)至3(完全丧失)的量表对肿瘤中血型抗原表达与正常表达的偏差进行量化。所有评分均与组织学分期和分级相关,提示形态学去分化与血型异常表达程度之间存在平行关系。在浅表性低级别肿瘤中,只有A和Lewis a评分与预后相关。这仅适用于A和Lewis a抗原表达正常或接近正常(评分为0和1)的肿瘤患者,他们在5年内侵袭性复发和/或乳头状瘤病方面病程良好。无法预测不良结局。只有少数浅表性肿瘤表现出正常的血型抗原表达。(摘要截断于400字)