17. MOLECULAR BIOLOGIC SUBSTAGING IN PATIENTS WITH STAGE I NON-SMALL CELL LUNG CANCER: RISK STRATIFICATION ACCORDING TO SEX AND HISTOLOGIC SUBTYPE
Thomas A. DÂ’Amico*, Thomas A. Aloia, Marga Massey, James E. Herndon, Mary-Beth Moore, and David H. Harpole
Duke University Medical Center
Durham, North Carolina, USA
BACKGROUND
Risk stratification using molecular markers in patients with stage I non-small cell lung cancer (NSCLC) has been demonstrated. This study assesses molecular biologic substaging according to sex and histologic subtypes, in order to determine the relative prognostic value of each variable and interactions among variables.
MATERIAL AND METHODS
Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I NSCLC at a single institution, with follow-up of at least 5 years. A panel of nine molecular markers (p53, erbB-2, Rb, bcl-2, EGFr, sialyl-Tn, CD-44, factor viii, and KI-67) was chosen for immunohistochemical analysis of the primary tumor. Cox proportional hazards regression analysis was used to construct an independent risk model for cancer-specific survival according to molecular marker status, sex, and histologic subtype.
RESULTS
A greater percentage of women had adenocarcinoma (87/139; 62%), and a greater percentage of men had squamous cell carcinoma (112/269; 45%; P=0.007). Among men, the only molecular marker associated with decreased cancer-specific survival was erbB-2 (P=0.0004); among women, there were 4 markers: p53 (P=0.0004); Rb (P=0.0004); CD-44 (P=0.03); and factor viii (P=0.03). Among patients with squamous cell carcinoma, the only molecular marker associated with decreased cancer-specific survival was erbB-2 (P=0.06); among patients with adenocarcinoma, there were 3 markers: p53 (P=0.0004); CD-44 (0.0001); and factor viii (P=0.02). Multivariable analysis of interactions among molecular markers, sex, and histology demonstrated two significant interactions associated with increased risk of death (hazard ratio): p53+/female (2.269) and CD-44+/adenocarcinoma (2.266).
CONCLUSIONS
Analysis of molecular biologic markers in this series of patients with NSCLC demonstrated differential expression and cancer-specific survival according to sex and histologic subtype. Further studies, designed to determine the molecular mechanisms of these relationships, are in progress.
