A biologic risk model for stage I lung cancer: Immunohistochemical analysis of 408 patients with the use of ten molecular markers

Objective: The standard treatment of patients with stage I non-small cell l ung cancer is resection of the primary tumor; however, the recurrence rate is 28% to 45%. This study evaluates a panel of molecular markers in a large population of patients with stage I non-small cell lung cancer to determin e the prognostic value of each marker and to create a biologic risk model. Methods: Pathologic specimens were collected From 408 consecutive patients after complete resection for stage I non-small cell lung cancer at a single institution, with follow-up of at least 5 years, A panel of 10 molecular m arkers was chosen for immunohistochemical analysis of the primary tumor on the basis of differing oncogenic mechanisms. Local tumor expansion requires growth regulating proteins (epidermal growth factor receptor, the protoonc ogene erb-b2); apoptosis proteins (p53, bcl-2); and cell cycle regulating p roteins (retinoblastoma recessive oncogene, KI-67), Local tumor invasion re quires angiogenesis (factor viii), The development of distant metastases in volves the expression of adhesion proteins (CD-44, sialyl-Tn, blood group A ). Cox proportional hazards regression analysis was used to construct an in dependent risk model for cancer recurrence and death. Results: Multivariabl e analysis demonstrated significantly elevated risk for the following molec ular markers: p53 (hazard ratio, 1.68; P = .004); factor viii (hazard ratio , 1.47; P = .033); erb-b2 (hazard ratio, 1.43; P = .044); CD-44 (hazard rat io, 1.40; P = .050); and retinoblastoma recessive oncogene (hazard ratio, 0 .747; P = .084), Conclusions: Five molecular markers were associated with t he risk of recurrence and death, representing independent metastatic pathwa ys: apoptosis (p53), angiogenesis (factor viii), growth regulation (erb-b2) , adhesion (CD-44), and cell cycle regulation (retinoblastoma recessive onc ogene), This study demonstrates the validity of this molecular biologic ris k model in patients with stage I nonsmall cell lung cancer.