Prognostic significance of tumor proliferative fraction and DNA content in stage I non-small cell lung cancer

Analyses of tumor DNA content and proliferative fraction by flow cytometry have been useful as prognostic determinants in a variety of solid tumors. The significance of this analysis in Stage I (T₁N₀M₀ and T₂N₀M₀) non-small cell lung carcinoma (NSCC) is unestablished. We determined DNA content (ploidy) and proliferative fraction (percentage S phase) on 44 surgically resected Stage I NSCC specimens obtained between 1977 and 1982. All cases had a minimum follow-up of 5 yr. Of the 44 cases, 27 were adenocarcinomas, 15 squamous cell carcinomas, and 2 large cell carcinomas. Of these, 32 (73%) had T₁N₀M₀ lesions and 12 (27%) had T₂N₀M₀ lesions. Overall 5-yr survival was 70%. All patients surviving 5 yr were free of detectable tumor. Patients with T₁N₀M₀ lesions had an 81% 5-yr survival, but those with T₂N₀M₀ lesions had a 42% 5-yr survival (p = 0.009). Analysis of tumor DNA content revealed 35 diploid tumors (79%) and 9 aneuploid tumors (21%). The 5-yr survival for diploid tumors was 77% compared with a 44% 5-yr survival in aneuploid lesions (p = 0.048). The median proliferative fraction was 6%. All patients with a percentage S phase less than 6% survived 5 yr, and 41% (9 of 22) of those greater than 6% survived 5 yr (p < 0.001). When 8% S phase was used as a cutoff, 93% (28 of 30) below the cutoff survived 5 yr but only 21% (3 of 14) above the cutoff survived 5 yr (p < 0.001). Within the T₁N₀M₀ subgroup (n = 32), all patients with a percentage S phase less than 6% survived past 5 yr but only 54% (7 of 13) of those greater than 6% survived 5 yr (p = 0.002). Thus, measurement of tumor proliferative fraction and, to a lesser extent DNA content, in Stage I NSCC may provide significant prognostic information apart from TNM stage and help identify a subset of patients at high risk for tumor relapse.