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

Abstract

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