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肾细胞癌中的细胞增殖。一项特别关注预后的临床研究。

Cell proliferation in renal cell carcinoma. A clinical study with special reference to prognosis.

作者信息

Larsson P

机构信息

Department of Urology, Umeå University, Sweden.

出版信息

Scand J Urol Nephrol Suppl. 1994;165:1-48.

PMID:7871395
Abstract

As the clinical behaviour of renal cell carcinoma (RCC) varies considerably from case to case, it is important to identify variables capable of predicting outcome in the individual patient. DNA ploidy status, analyzed by flow cytometry (FCM) in 59 patients with stage I disease, showed survival to be significantly better in the diploid than in the non-diploid subgroup. The prognostic value of S-phase fraction evaluated from DNA histograms (S-FCM) was studied in 69 RCC patients. The mean S-phase value was 7.5%, the values being significantly lower in the diploid than in the aneuploid subgroup. Both in the group as a whole and among patients with aneuploid tumors, survival was significantly better in the low (< 7.5%) than in the high (> or = 7.5%) S-phase fraction subgroup. Multivariate analysis showed both the S-phase fraction and tumor stage to be significant independent prognostic variables. Immunohistochemistry (IHC) studies with in vivo iododeoxyuridine labeling (IdUrd-IHC) performed in a series of 33 RCC patients, showed a mean labelling index (LI) of 1.06%. The LI values being significantly lower in diploid than in aneuploid tumors. In a series of 29 RCC patients cell kinetic studies with in vivo IdUrd labeling and subsequent FCM analysis (IdUrd-FCM), showed a mean tumor LI of 2.7%, and a mean potential tumor doubling time (Tpot) of 20.3 days (kidney cortex samples 137.7 days). Tpot was found to be a significant prognostic indicator, though as intratumor heterogeneity in Tpot was common it needs to be determined in multiple samples. Proliferating cell nuclear antigen (PCNA) expression evaluated by IHC using the monoclonal antibody PC-10 (PCNA-IHC) in 68 RCC patients, showed the mean PCNA index to be 4.9%, and values being significantly greater in aneuploid than in diploid tumors. Both in the group as a whole and among patients with non-metastatic disease, survival was better in the low (< 3.5%) than in the high (> or = 3.5%) PCNA index subgroup. Four different methods of cell proliferation (S-FCM, IdUrd-IHC, IdUrd-FCM, PCNA-IHC) were compared. Comparative analysis according to the Bland and Altman method, showed a good degree of agreement. The results indicated that the different methods seemed to provide comparable information on proliferative activity, although different cell-cycle compartments were monitored.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

由于肾细胞癌(RCC)的临床行为在不同病例之间差异很大,因此识别能够预测个体患者预后的变量非常重要。对59例I期疾病患者进行流式细胞术(FCM)分析的DNA倍体状态显示,二倍体亚组的生存率明显高于非二倍体亚组。在69例RCC患者中研究了从DNA直方图评估的S期分数(S-FCM)的预后价值。平均S期值为7.5%,二倍体亚组的值明显低于非整倍体亚组。在整个组以及非整倍体肿瘤患者中,S期分数低(<7.5%)的亚组的生存率明显高于高(>或=7.5%)S期分数亚组。多变量分析显示S期分数和肿瘤分期都是重要的独立预后变量。对33例RCC患者进行体内碘脱氧尿苷标记(IdUrd-IHC)的免疫组织化学(IHC)研究显示,平均标记指数(LI)为1.06%。二倍体肿瘤中的LI值明显低于非整倍体肿瘤。在29例RCC患者中进行体内IdUrd标记及随后的FCM分析(IdUrd-FCM)的细胞动力学研究显示,平均肿瘤LI为2.7%,平均潜在肿瘤倍增时间(Tpot)为20.3天(肾皮质样本为137.7天)。尽管Tpot在肿瘤内的异质性很常见,需要在多个样本中确定,但发现Tpot是一个重要的预后指标。使用单克隆抗体PC-10通过IHC评估68例RCC患者的增殖细胞核抗原(PCNA)表达(PCNA-IHC)显示,平均PCNA指数为4.9%,非整倍体肿瘤中的值明显高于二倍体肿瘤。在整个组以及非转移性疾病患者中,PCNA指数低(<3.5%)的亚组的生存率高于高(>或=3.5%)PCNA指数亚组。比较了四种不同的细胞增殖方法(S-FCM、IdUrd-IHC、IdUrd-FCM、PCNA-IHC)。根据布兰德和奥特曼方法进行的比较分析显示出良好的一致性。结果表明,尽管监测的是不同的细胞周期区室,但不同方法似乎提供了关于增殖活性的可比信息。(摘要截断于400字)

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