Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer

Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):787-96. doi: 10.1016/s0360-3016(97)00898-5.


Purpose: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined.

Materials & methods: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes.

Results: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (p = 0.002), and distant metastasis control (p = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p = 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04).

Conclusion: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less distant metastasis better DFS and overall survival than those with AC. Multivariate analysis revealed that DNA index and Ki-67 status were significant predictors for DDC and DFS in patients with AC, but only mitotic index was a significant predictor of overall survival for patients with SCC.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / secondary
  • Analysis of Variance
  • Apoptosis
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • DNA, Neoplasm / analysis
  • Female
  • Follow-Up Studies
  • Genetic Markers
  • Humans
  • Ki-67 Antigen / analysis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mitotic Index
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies


  • Biomarkers
  • DNA, Neoplasm
  • Genetic Markers
  • Ki-67 Antigen