Prognostic value of cytokeratin-positive cells in the bone marrow and lymph nodes of patients with resected nonsmall cell lung cancer: a multicenter prospective study

BACKGROUND: This study was designed to prospectively substantiate the prognostic value of cytokeratin-positive (CK(+)) cells in the bone marrow (BM) and regional lymph nodes (LNs) in resected nonsmall cell lung cancer (NSCLC) patients from a large population within a multicenter study. METHODS: The study population consisted of 351 patients with stages I to IIIA NSCLC from 15 Japanese institutes. BM aspirates were stained immunocytochemically with the anti-cytokeratin antibody, CK2. The hilar and mediastinal LNs of 216 patients with stage I NSCLC were stained immunohistochemically with the anti-CK antibody, AE1/AE3. RESULTS: CK(+) cells were detected in 112 patients (31.9%) of the 351 BM aspirate patients. The frequency of CK(+) cells showed no differences among pathologic stages. The patients with CK(+) cells in the BM had a tendency to have shorter survival periods than those without CK(+) cells (p = 0.076). Although the presence of CK(+) cells in the BM of patients with stage I did not allow the prediction of overall survival, it reduced the overall survival significantly in patients with stages II to IIIA. CK(+) cells in the LNs were detected in 34 of 216 patients (15.7%) with stage I. The patients with CK(+) cells in the LNs had a poor prognosis by both univariate (p = 0.004) and multivariate analyses (p = 0.018). CONCLUSIONS: The presence of CK(+) cells in the BM was related to a poor prognosis for patients with stages II to IIIA NSCLC; however, it did not predict the prognosis of patients with stage I. For stage I NSCLC, the detection of CK(+) cells in the LNs implied a poor prognosis for the patients.