Analysis of Histopathological Heterogeneity of Urinary Bladder Cancer by Molecular Biological Technique.

1. c-erbB-2基因产物在人尿路移行细胞癌的免疫电镜下被证实。单克隆抗体的免疫反应局限于细胞膜，呈线性模式。细胞间隙中的无定形沉积物也与针对细胞外表位的单克隆抗体产生免疫反应，这表明部分c-erbB-2基因产物可能从癌细胞膜释放到细胞外空间。用免疫组织学和Western blot方法研究了c-erbB-2基因产物和表皮生长因子受体（EGF-R）在人膀胱癌组织中的表达。c-erbB-2基因产物在高级别肿瘤和高分期肿瘤中表达更为频繁。而EGF-R的表达与这两个参数无关。这些结果表明，c-erbB-2可能与EGF-R在控制癌细胞的某些特异性反应中起着不同的作用，也可能更多地作为恶性肿瘤的制造者。在移行细胞癌石蜡包埋组织标本中，免疫组织学检测到cerbB-2基因产物的表达。该染色阳性率为26%。cerbB-2阳性肿瘤患者的5年生存率明显短于cerbB-2阴性肿瘤患者（p<0.05）。从cerbB-2阳性标本中提取的基因组DNA进行斑点杂交分析表明，该基因在所有cerbB-2阳性癌症患者中均未扩增。这些结果提示cerbB-2的表达可作为人类移行性癌的潜在恶性肿瘤标志物和预后因素。用单克隆抗体MRK-16在正常肾脏中定位人多药耐药基因mdr1产物。肾细胞癌和膀胱癌。mdr1基因产物定位于细胞膜上，其表达率与组织学分级无相关性。癌症家族综合征兄弟姐妹的癌基因扩增。其中4 / 7的孩子在50岁前从胃肠道和/或泌尿生殖器官发生了1 - 3种原发性癌。用石蜡包埋块制备的DNA进行了检测。在来自3个兄弟姐妹的8个肿瘤中，1个扩增了H-ras， 6个扩增了c-myc， 1个扩增了c-erbB-2。该癌症家族的致癌基因扩增可能是遗传易感性的结果，可能促进了这些肿瘤的早期表现。少

1. The c-erbB-2 gene product was demonstrated immunoelectron microscopically in human transitional cell carcinomas of the urinary tract. The immune reaction with the monoclonal antibody was confined to cell membranes with a linear pattern. Amorphous deposits in the intercellular spaces were also immunoreactive with the monoclonal antibody directed to an extracellular epitope, suggesting that a part of the c-erbB-2 gene product may be released from the cancer cell membranes into the extracellular space.2. Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in human bladder cancer immunohistologically and by Western blot analysis. The c-erbB-2 gene product was more frequently expressed in high grade tumors and in high stage tumors. while the expression of EGF-R was independent of these two parameters. These results suggest that c-erbB-2 may play a different role from EGF-R to control some specific reaction of cancer cell, also it may … More be used as a tumor maker for the malignant potential.3. Expression of cerbB-2 gene product could be detected immunohistologically in paraffin-embeddedtissue specimen of transitional cell carcinoma. Positive rate of this staining was 26%. Five year survival rate of patients with cerbB-2 positive cancer was significantly shorter than that of patients with cerbB-2 negative cancer (p<0.05). Dot blot hybridization analysis using genomic DNA extracted from the cerbB-2 positive specimen demonstrated that the gene was not amplified in all patients with cerbB-2 positive cancer.These results suggest that cerbB-2 expression may be applicable as a tumor marker of malignant potential and prognostic factor of human transitional carcinoma.4. Localization of product of the human mdr1 standing for multidrug resistant gene was investigated with monoclonal antibody MRK-16 in normal kidney. Renal cell cancer and urinary bladder cancer. The mdr1 gene product was localized on cell membrane and there was no correlation between its expression rate and histological grading.5. Oncogene amplication in siblings of cancer family syndrome. In which 4 of 7 sidlings developed 1 to 3 primary carcinomas from the gastrointestinal and/or genitourinary organs before 50-year old. Was surveyed using DNA prepared from paraffin- embedded block. Of 8 tumors from 3 siblings H-ras was amplified in 1, c-myc in 6 and c-erbB-2 in 1. The oncogene amplification in this cancer family would be a consequence of hereditary predisposition and may have promote the early manifestation of these tumors. Less