Benini E, Costa A, Pizzocaro G, Campo B, Milani A, Torelli T, Veneroni S, Ordesi G, Pilotti S, Silvestrini R
IST NAZL STUDIO & CURA TUMORI,VIA VENEZIAN 1,I-20133 MILAN,ITALY. OSPED PREDABISSI,MELEGNANO,ITALY.
Int J Oncol. 1993 Nov;3(5):817-21. doi: 10.3892/ijo.3.5.817.
A biologic profile including proliferative.activity, evaluated as H-3-thymidine labeling index (H-3-dT LI), DNA ploidy, p53 tumor-suppressor gene and P-glycoprotein (P-170), as an expression of the multidrug resistance gene, was defined for 50 primary transitional cell carcinomas of the bladder. H-3-dT LI was evaluated by autoradiography on histologic sections after incubation of fresh tumor biopsies with H-3-thymidine. Ploidy was defined by flow cytometric analysis of DNA content on nuclei suspensions obtained from frozen material. Expression of p53 protein and P-170 glycoprotein was detected by immunohistochemistry using the PAb1801 and C219 monoclonal antibody respectively, on sections from paraffin-embedded tumor biopsies. Invasive tumors showed a higher median H-3-dT LI (12.7% vs 4.2%) and a higher frequency of aneuploidy (73% vs 43%) and more frequently expressed p53 (82% vs 36%) than superficial tumors. Further analysis showed that proliferative activity was higher in invasive than in superficial cancers only in p53-positive or aneuploid tumors and not in p53-negative or diploid tumors. Moreover, proliferative activity and p53 overexpression, but not ploidy, were directly related to histologic grading and tumor stage. Generally, P-170 was not significantly related to any biologic or clinico-pathologic factor. Kinetic and phenotypic biologic markers are differently related to clinico-pathologic factors. A panel of biologic features can be easily evaluated on small transurethral biopsies at diagnosis, during endocavitary treatment or follow-up in bladder cancer patients.
对50例原发性膀胱移行细胞癌进行了生物学特征分析,包括增殖活性(以H-3-胸腺嘧啶核苷标记指数(H-3-dT LI)评估)、DNA倍体、p53肿瘤抑制基因以及作为多药耐药基因表达形式的P-糖蛋白(P-170)。在新鲜肿瘤活检标本与H-3-胸腺嘧啶核苷孵育后,通过组织学切片放射自显影评估H-3-dT LI。通过对从冷冻材料获得的细胞核悬液进行DNA含量的流式细胞术分析来确定倍体。分别使用PAb1801和C219单克隆抗体,通过免疫组织化学在石蜡包埋肿瘤活检标本的切片上检测p53蛋白和P-170糖蛋白的表达。浸润性肿瘤与浅表性肿瘤相比,具有更高的中位H-3-dT LI(12.7%对4.2%)、更高的非整倍体频率(73%对43%),并且更频繁地表达p53(82%对36%)。进一步分析表明,仅在p53阳性或非整倍体肿瘤中,浸润性癌的增殖活性高于浅表性癌,而在p53阴性或二倍体肿瘤中并非如此。此外,增殖活性和p53过表达而非倍体与组织学分级和肿瘤分期直接相关。一般来说,P-170与任何生物学或临床病理因素均无显著相关性。动力学和表型生物学标志物与临床病理因素的关系不同。在膀胱癌患者诊断时、腔内治疗期间或随访时,通过小的经尿道活检标本就可以轻松评估一组生物学特征。