细胞核DNA含量衍生参数与透明细胞肾细胞癌中p53和bcl-2蛋白的异质性表达相关。

Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas.

作者信息

Pepe S, Ruggiero A, D'Acquisto M, De Laurentiis M, De Placido S, Sandomenico C, Staibano S, De Rosa G, Lucariello A, D'Armiento M, Bianco A R

机构信息

Department of Molecular and Clinical Endocrinology and Oncology, University "Federico II," Naples, Italy.

出版信息

Cancer. 2000 Sep 1;89(5):1065-75. doi: 10.1002/1097-0142(20000901)89:5<1065::aid-cncr16>3.0.co;2-t.

DOI:10.1002/1097-0142(20000901)89:5<1065::aid-cncr16>3.0.co;2-t

PMID:10964337

Abstract

BACKGROUND

p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF.

METHODS

Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry.

RESULTS

In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32 (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P = 0. 03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P < 0. 0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P < 0.0001) and low SPF (P = 0. 035).

CONCLUSIONS

Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF.

摘要

背景

p53和bcl-2是参与细胞周期和细胞死亡调控的两个关键基因。在人类癌症中已发现这些基因的表达改变或突变，在透明细胞肾细胞癌（RCC）中也已得到确认。然而，它们在RCC进展中的作用仍不清楚。相比之下，RCC中倍体和S期分数（SPF）的预后意义已得到广泛研究。为了更好地描述p53和bcl-2癌蛋白在RCC中的生物学作用，我们对这两种蛋白的表达与倍体和SPF进行了多样本相关性分析。

方法

对33例连续可手术切除的RCC进行多次采样，选取296个标本，分析其倍体、SPF以及p53和bcl-2的表达情况。通过免疫组织化学研究p53和bcl-2蛋白的表达，通过流式细胞术研究SPF和肿瘤倍体。

结果

在我们的研究中，32例中有4例（12.5%）为二倍体，32例中有28例（87.5%）显示DNA含量异常。在非整倍体肿瘤中，28例中有14例（50%）为多倍体。32例肿瘤中有21例（65.6%）检测到异质性DNA含量，且与更晚期的Robson分期肿瘤相关（P = 0.03）。p53和bcl-2蛋白表达也检测到肿瘤内异质性。p53蛋白表达与bcl-2蛋白表达缺失（P = 0.0032）、非整倍体（P < 0.0001）和高SPF（P = 0.0006）相关，而bcl-2表达与正常DNA含量（P < 0.0001）和低SPF（P = 0.035）相关。