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

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.