脱氧核糖核酸（DNA）图像分析细胞术及Ki67免疫组化表达对手术切除的非小细胞肺癌的预后影响

Prognostic impact of Deoxyribonucleic acid (DNA) image analysis cytometry and immunohistochemical expression of Ki67 in surgically resected non-small cell lung cancers.

作者信息

Maounis Nicoletta F, Chorti Maria, Apostolakis Efstratios, Ellina Eleni, Blana Aikaterini, Aggelidou Maria, Dritsas Ioannis, Markidou Sophia

机构信息

Department of Cytology, Sismanoglion General Hospital, 1 Sismanogliou Str., Athens 151 26, Greece.

出版信息

Cancer Detect Prev. 2006;30(6):507-14. doi: 10.1016/j.cdp.2006.07.007. Epub 2006 Nov 20.

DOI:10.1016/j.cdp.2006.07.007

PMID:17113721

Abstract

BACKGROUND

The aim of the present study was to evaluate the prognostic significance of DNA ploidy and Ki67 expression in non-small cell lung carcinoma (NSCLC).

METHODS

This prospective study included 96 patients with stages I-IIIA NSCLC who underwent surgical excision. DNA image analysis cytometry was applied on imprints. Calculation of the DNA index (DI) and the 5c exceeding rate (5cER) was performed and the histograms were classified as peridiploid, peritetraploid, and x-ploid-multiploid. The Ki67 immunoreactivity was determined according to the avidin-biotin complex immunoperoxidase method.

RESULTS

DNA histogram classification disclosed 30 peridiploid cases, 15 peritetraploid and 51 x-ploid-multiploid. Forty-eight cases (50%) had 5cER > 5%. The Ki67 immunoreactivity was below 25% in 53 tumors (62.4%) and above 25% in 32 (32.6%). Our results revealed the existence of a statistically significant relationship of DNA ploidy with nodal status (p = 0.042) and grade (p = 0.005). Adenocarcinomas and large cell carcinomas were more frequently encountered in x-ploid-multiploid tumors as compared to squamous cell carcinomas, which were more frequently peridiploid (p = 0.003). 5cER showed statistically significant association with nodal status (p = 0.037). Univariate analysis with respect to survival revealed significant association with stage (p < 0.001), nodal status (p < 0.001), tumor status (p < 0.001), DNA ploidy (p = 0.008) and 5cER (p = 0.0124). Multivariate analysis revealed stage and ploidy status as independent factors: peridiploid tumors were associated with better survival as compared to x-ploid-multiploid tumors (p = 0.022).

CONCLUSION

Our results suggest that DNA ploidy, as determined by image analysis, provides an independent prognostic parameter for patients with NSCLC and thus, could be used to identify a subset of patients with more aggressive tumors.

摘要

背景

本研究旨在评估DNA倍体和Ki67表达在非小细胞肺癌（NSCLC）中的预后意义。

方法

这项前瞻性研究纳入了96例接受手术切除的I-IIIA期NSCLC患者。对印片进行DNA图像分析细胞术。计算DNA指数（DI）和5c超标率（5cER），并将直方图分类为亚二倍体、亚四倍体和异倍体-多倍体。根据抗生物素蛋白-生物素复合物免疫过氧化物酶法测定Ki67免疫反应性。

结果

DNA直方图分类显示30例亚二倍体病例，15例亚四倍体和51例异倍体-多倍体。48例（50%）5cER>5%。53例肿瘤（62.4%）的Ki67免疫反应性低于25%，32例（32.6%）高于25%。我们的结果显示DNA倍体与淋巴结状态（p = 0.042）和分级（p = 0.005）存在统计学显著关系。与鳞状细胞癌相比，异倍体-多倍体肿瘤中腺癌和大细胞癌更常见，鳞状细胞癌更常见为亚二倍体（p = 0.003）。5cER与淋巴结状态存在统计学显著关联（p = 0.037）。关于生存的单因素分析显示与分期（p < 0.001）、淋巴结状态（p < 0.001）、肿瘤状态（p < 0.001）、DNA倍体（p = 0.008）和5cER（p = 0.0124）存在显著关联。多因素分析显示分期和倍体状态为独立因素：与异倍体-多倍体肿瘤相比，亚二倍体肿瘤与更好的生存相关（p = 0.022）。