Nemoto R, Uchida K, Shimazui T, Hattori K, Koiso K, Harada M
Department of Urology, University of Tsukuba, Ibaraki, Japan.
J Urol. 1989 Feb;141(2):337-40. doi: 10.1016/s0022-5347(17)40760-9.
Using a monoclonal antibody to bromodeoxyuridine and immunohistochemistry, we measured the incorporation of this thymidine analogue into the deoxyribonucleic acid of human prostate adenocarcinoma cells exposed in situ. Fifteen patients with prostate cancer were given an intravenous infusion of 500 mg. bromodeoxyuridine at needle biopsy to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method using anti-bromodeoxyuridine monoclonal antibody as the first antibody. The results showed that this method demonstrated bromodeoxyuridine-labeled nuclei satisfactorily in tissue section. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. Grade 3 tumors averaged 4.37 +/- 0.48 per cent labeling versus 2.41 +/- 0.49 per cent in grade 2 tumors, and grade 1 tumor in the series had an S phase fraction of 1.36 +/- 0.39 per cent. The average S phase fractions for single gland, cribriform, fused and medullary were 1.16, 2.30, 3.74 and 4.95 per cent, respectively. The results obtained with S phase fraction measured with bromodeoxyuridine labeling proved to be comparable to the results of histological grade and growth pattern. Thus, the higher S phase fraction may indicate biological malignancy. Moreover, the degree of heterogeneity concerning S phase fraction distribution within prostate cancer tissue could be compared to the morphological appearance. Our preliminary results suggest that the measurement of bromodeoxyuridine labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.
我们使用针对溴脱氧尿苷的单克隆抗体及免疫组织化学方法，测定了这种胸苷类似物原位掺入人前列腺腺癌细胞脱氧核糖核酸的情况。15例前列腺癌患者在针吸活检时静脉输注500mg溴脱氧尿苷，以标记处于脱氧核糖核酸合成期（S期）的肿瘤细胞。肿瘤标本用70%乙醇固定，石蜡包埋，切片，并用抗溴脱氧尿苷单克隆抗体作为一抗的间接免疫过氧化物酶法染色。结果显示，该方法能在组织切片中令人满意地显示出溴脱氧尿苷标记的细胞核。通过计数组织切片中溴脱氧尿苷标记的细胞数量来确定溴脱氧尿苷标记指数，即S期分数。3级肿瘤的平均标记率为4.37±0.48%，而2级肿瘤为2.41±0.49%，该系列中的1级肿瘤S期分数为1.36±0.39%。单腺型、筛状型、融合型和髓样型的平均S期分数分别为1.16%、2.30%、3.74%和4.95%。用溴脱氧尿苷标记测得的S期分数结果与组织学分级和生长模式的结果具有可比性。因此，较高的S期分数可能表明生物学恶性程度较高。此外，前列腺癌组织内S期分数分布的异质性程度可与形态学表现相比较。我们的初步结果表明，测定前列腺癌中的溴脱氧尿苷标记指数可能成为一种新的、客观且定量的个体肿瘤生物学潜能检测方法。
