Predicting the sites of metastases from lung cancer using molecular biologic markers

Background. The use of molecular markers in staging non-small cell lung can cer (NSCLC) has been supported in retrospective prognostic models but has n ot been evaluated in predicting sites of metastases. Methods. Pathologic specimens were collected from 202 patients after comple te resection for stage I NSCLC, who were subsequently found to have no meta stases at 5 years (n = 108), isolated brain metastases (n = 25), or other d istant metastases (n = 69). A panel of eight molecular markers of metastati c potential was chosen for immunohistochemical analysis of the tumor: p53, erbB2, angiogenesis factor viii, EphA2, E-cadherin, urokinase plasminogen a ctivator (UPA), UPA receptor, and plasminogen activator inhibitor. Results. Patients with isolated brain relapse had significantly higher expr ession of p53 (p = 0.02) and UPA (p = 0.002). The quantitative expression o f E-cadherin was used to predict the site of metastases using recursive par titioning: 0 of 92 patients with E-cadherin expression of 0, 1, or 2 develo ped isolated cerebral metastases; 0 of 33 patients with E-cadherin expressi on of 3 with UPA of 1 or 2 and ErbB2 of 0 developed brain metastases. Of th e remaining patients at risk (UPA = 3), the risk of isolated cerebral metas tases was 21 of 57 patients (37%). Conclusions. This study demonstrates that molecular markers may predict the site of relapse in early stage NSCLC. If validated in an ongoing prospecti ve study, these results could be used to select patients with isolated brai n metastases for adjuvant therapy, such as prophylactic cranial irradiation . (C) 2001 by The Society of Thoracic Surgeons.