增殖细胞核抗原和Ki-67在肺癌中的表达及其与DNA流式细胞术分析的相关性

Proliferating cell nuclear antigen and Ki-67 in lung carcinoma. Correlation with DNA flow cytometric analysis.

作者信息

Kawai T, Suzuki M, Kono S, Shinomiya N, Rokutanda M, Takagi K, Ogata T, Tamai S

机构信息

Department of Pathology, National Defense Medical College, Tokorozawa, Japan.

出版信息

Cancer. 1994 Nov 1;74(9):2468-75. doi: 10.1002/1097-0142(19941101)74:9<2468::aid-cncr2820740913>3.0.co;2-x.

DOI:10.1002/1097-0142(19941101)74:9<2468::aid-cncr2820740913>3.0.co;2-x

PMID:7923002

Abstract

BACKGROUND

To study the prognosis of patients with lung carcinomas, the efficacy of proliferating cell nuclear antigen (PCNA) in ensuring both the proliferative activity defined using Ki-67 labeling and the cell cycle data obtained using flow cytometry was determined.

METHODS

The authors used immunostaining to study frozen and paraffin embedded sections of 165 surgically resected lung carcinomas [squamous cell carcinoma, n = 84; adenocarcinoma, n = 62; large cell carcinoma, n = 15; small cell carcinoma, n = 4] for the presence of PCNA and Ki-67 antibodies. Also studied were two parameter flow cytometric analysis of fluorescein isothiocyanate conjugated PCNA/propidium iodide for 165 fresh frozen tissues. Clinicopathologic data (sex, age, tumor stage, survival period, histologic type, degree of cell differentiation, and cellularity) were evaluated using the Statistical Analysis System.

RESULTS

The percentages of PCNA positive cells per 1000 nuclei were 52% of squamous cell carcinoma; 49% in adenocarcinomas; 76% of large cell carcinoma; and 63% of small cell carcinoma. Positive PCNA staining was significantly correlated with stage, cellularity, and DNA index. Calculation of logistic regression coefficients indicated an association between overall survivals and tumor cellularity (P < 0.0003), percentage of cells stained with PCNA antibody (P < 0.02), DNA pattern (aneuploid versus diploid) (P < 0.009), DNA index (P < 0.009), and percentage of cells in S-phase (P < 0.04). Both cellularity (P = 0.03) and DNA (P = 0.08) retained its independent level of significance by multivariate analysis.

CONCLUSIONS

In addition to clinical stage and histologic differentiation, both cellularity and DNA content may help predict the course of lung carcinomas.

摘要

背景

为研究肺癌患者的预后，确定增殖细胞核抗原（PCNA）在确保使用Ki-67标记定义的增殖活性和使用流式细胞术获得的细胞周期数据方面的有效性。

方法

作者使用免疫染色研究了165例手术切除肺癌（鳞状细胞癌，n = 84；腺癌，n = 62；大细胞癌，n = 15；小细胞癌，n = 4）的冰冻切片和石蜡包埋切片中PCNA和Ki-67抗体的存在情况。还对165份新鲜冰冻组织进行了异硫氰酸荧光素偶联PCNA/碘化丙啶的双参数流式细胞术分析。使用统计分析系统评估临床病理数据（性别、年龄、肿瘤分期、生存期、组织学类型、细胞分化程度和细胞密度）。

结果

每1000个细胞核中PCNA阳性细胞的百分比在鳞状细胞癌中为52%；腺癌中为49%；大细胞癌中为76%；小细胞癌中为63%。PCNA阳性染色与分期、细胞密度和DNA指数显著相关。逻辑回归系数计算表明总生存期与肿瘤细胞密度（P < 0.0003）、PCNA抗体染色细胞百分比（P < 0.02）、DNA模式（非整倍体与二倍体）（P < 0.009）、DNA指数（P < 0.009）和S期细胞百分比（P < 0.04）之间存在关联。通过多变量分析，细胞密度（P = 0.03）和DNA（P = 0.08）均保持其独立的显著性水平。