Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis

Chest. 2003 Jun;123(6):1858-67. doi: 10.1378/chest.123.6.1858.

Abstract

Study objective: To evaluate the prognostic value of histopathologic variables and molecular markers in a group of patients with stage I non-small cell lung cancer (NSCLC).

Setting: "María Ferrer" Hospital of Buenos Aires, Argentina.

Patients: Pathologic stage IA and IB patients who underwent radical surgery and nonneoadjuvant therapy for NSCLC between January 1985 and December 1999.

Measurements and results: Fifty-three patients fulfilling the inclusion criteria were identified. The overall survival was 52.8%, and 28% of patients had recurrent disease. We found significant differences between squamous cell carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0.001) and lymphatic permeation (p = 0.01). SCCs showed higher proliferation (MIB-1 grades 2 and 3) [p = 0.001], Bcl-2 expression (p = 0.038), and CD44 expression (p = 0.019) than adenocarcinomas. The log-rank test showed that mitosis count, necrosis, MIB-1, and Bcl-2 were predictive factors for relapse. All of them were associated with increased relapse and a shorter time to recurrence. Multivariate analysis using the Cox proportional hazards regression model showed that mitosis count, Bcl-2 expression, and grade 3 of MIB-1 emerged as independent prognostic factors of recurrence.

Conclusions: We found that mitosis count and MIB-1 expression had significant value to predict recurrence, reflecting the aggressiveness of high-rate proliferative tumors. We could also show that patients with positive Bcl-2 tumors had a poor outcome, probably related to the uncontrolled cell growth that the expression of Bcl-2 promotes. Our observations are of potential interest for the development of rational postresection treatment strategies based on the estimated risk of recurrence of patients with NSCLC.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Humans
  • Hyaluronan Receptors / analysis
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mitosis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Hyaluronan Receptors
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2