Background. This study is designed to assess molecular biologic substaging
according to gender and histology in patients with stage I non-small cell l
ung cancer (NSCLC).
Methods. Pathologic specimens were collected from 408 consecutive patients
after complete resection for stage I NSCLC, with follow-up of at least 5 ye
ars. A panel of nine molecular markers was chosen for immunohistochemical a
nalysis of the tumor recessive oncogenes p53 and bcI-2, the protooncogene e
rbB-2, KI-67 proliferation index, retinoblastoma oncogene (Rb), epidermal g
rowth factor receptor (EGFr), angiogenesis factor viii, sialyl-Tn antigen (
STN), and CD-44. Cox proportional hazards regression analysis was used to c
onstruct a risk model for cancer-specific survival according to marker stat
us, gender, and histologic subtype.
Results. Among men, the only molecular marker associated with decreased can
cer-specific survival is erbB-2; among women, there are four markers: p53,
Rb, CD-44, and factor viii, Among patients with squamous cell carcinoma the
only molecular marker associated with decreased cancer-specific survival i
s erbB-2; among patients with adenocarcinoma (AC), there are three markers:
p53, CD-44, and factor viii. Multivariable analysis of interactions among
molecular markers, gender, and histology demonstrates two important relatio
nships (hazard. ratio): p53+/women (2.269) and CD-44+/AC (2.266).
Conclusions. Molecular biologic substaging of patients with stage I NSCLC d
emonstrates differential cancer-specific survival according to marker expre
ssion, gender, and histologic subtype.