Kimura E, Enns R E, Alcaraz J E, Arboleda J, Slamon D J, Howell S B
Department of Medicine, University of California San Diego, La Jolla 92093-0812.
J Clin Oncol. 1993 May;11(5):891-8. doi: 10.1200/JCO.1993.11.5.891.
Ovarian carcinomas express the 60-kD heat-shock protein HSP-60 at widely varying levels in different tumors. The aim of this study was to determine whether there was a relationship between expression of HSP-60 and survival in patients with ovarian carcinoma.
Total RNA and DNA were prepared from 51 epithelial ovarian cancer tissue samples. The expression and structure of the HSP-60 gene were examined by Northern and Southern blot analyses using the carboxyl-terminal portion of this gene as a probe (0.89 kilobases [kb]). HSP-60 expression was correlated with overall survival by the Kaplan-Meier method.
The 2.3-kb HSP-60 message was detected in all samples, but there was marked variation from tumor to tumor. Patients were classified into two groups on the basis of HSP-60 expression: group 1 (n = 25) included patients with low expression, and group 2 (n = 26) consisted of patients with high expression. There were no significant differences between the groups with respect to age, cell type, pathologic grade, clinical stage, and previous treatment. After a median follow-up period of 17 months, Kaplan-Meier plots demonstrated a much better survival for group 1 (median, 46.8 months; 41% at 4 years) than group 2 (median, 22.1 months; 16% at 3.9 years), a difference that was highly significant by the Mantel-Haenszel test (P = .00183). Southern blot analysis of these samples showed no amplification or rearrangement of the gene.
The level of HSP-60 mRNA expression is a valuable prognostic factor in epithelial ovarian cancer. Variation in the level of expression is not due to amplification of this gene.
卵巢癌在不同肿瘤中表达60-kD热休克蛋白HSP-60的水平差异很大。本研究的目的是确定HSP-60的表达与卵巢癌患者生存率之间是否存在关联。
从51份上皮性卵巢癌组织样本中提取总RNA和DNA。使用该基因的羧基末端部分作为探针(0.89千碱基[kb]),通过Northern和Southern印迹分析检测HSP-60基因的表达和结构。采用Kaplan-Meier法将HSP-60表达与总生存率进行关联分析。
在所有样本中均检测到2.3-kb的HSP-60信使RNA,但肿瘤之间存在明显差异。根据HSP-60表达将患者分为两组:第1组(n = 25)包括低表达患者,第2组(n = 26)由高表达患者组成。两组在年龄、细胞类型、病理分级、临床分期和既往治疗方面无显著差异。中位随访期为17个月后,Kaplan-Meier曲线显示第1组(中位生存期,46.8个月;4年时为41%)的生存率远高于第2组(中位生存期,22.1个月;3.9年时为16%),Mantel-Haenszel检验显示该差异具有高度显著性(P = .00183)。对这些样本进行Southern印迹分析未发现该基因的扩增或重排。
HSP-60 mRNA表达水平是上皮性卵巢癌的一个有价值的预后因素。表达水平的差异并非由于该基因的扩增所致。