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Prognostic Impact of Micrometastatic Tumor Cells in the Lymph Nodes and Bone Marrow of Patients With Completely Resected Stage I Non–Small-Cell Lung Cancer

From the Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Address reprint requests to Toshihiro Osaki, MD, Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan; email: t-osaki{at}med.uoeh-u.ac.jp

PURPOSE: This study was designed to substantiate the prognostic impact of occult micrometastatic tumor cells in the lymph nodes (LNs) and bone marrow (BM) in stage I non–small-cell lung cancer (NSCLC) patients using cytokeratin (CK) as a micrometastatic marker and the relationship between the micrometastases in the LNs and BM.

PATIENTS AND METHODS: A total of 2,432 hilar and mediastinal LNs were removed during surgery from 115 patients with completely resected stage I NSCLC. The LNs were analyzed for micrometastasis using immunohistochemistry with the biclonal anti-CK antibody AE1/AE3. BM aspirates from 115 patients were immunocytochemically stained with the monoclonal anti-CK antibody CK2.

RESULTS: CK-positive (CK+) cells were detected in 42 (1.7%) of 2,432 LNs, in 32 (27.8%) of 115 patients, and in 32 (27.8%) of 115 BM aspirates. There was no relationship between the frequencies of CK+ cells in the LNs and in the BM. The patients with CK+ cells in the LNs had a poor prognosis by both univariate (P = .008) and multivariate analyses (P = .01), whereas the presence of CK+ cells in the BM did not allow prediction of survival (P = .32). The prognostic impact of LNs micrometastasis was independent even after adjusting for the status of BM micrometastasis.

CONCLUSION: The detection of lymph nodal micrometastatic tumor cells provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients.

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