The presence of occult micrometastases (OM) by immunohistochemistry (IHC) staining in N2 lymph nodes of patients with stage 1 non-small cell lung cancer (NSCLC) was linked to decreased overall survival, according to a study published in the Journal of Clinical Oncology.1

The Cancer and Leukemia Group B 9761 conducted a prospectively designed study to determine the prognostic significance of OM because undetected OM could potentially be a prognostic indicator of outcomes following resection of stage 1 NSCLC.

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A total of 502 patients with suspected clinical stage 1 (T1-2N0M0) NSCLC were enrolled in the study. Molecular analysis was performed on primary tumor sites and lymph nodes. Both were assayed for OM using IHC for cytokeratin and real-time reverse transcriptase polymerase chain reaction (PCR) for carcinoembryonic antigen.

Of the 502 patients, 498 underwent complete surgical staging. Results showed that 304 patients (61%) had pathologic stage 1 NSCLC (T1, 58%; T2, 42%) and were included in the final analysis.

IHC was used to analyze lymph nodes from 298 patients: 41 (14%) were IHC-positive (42% in N1 position; 58% in N2 position). IHC-positivity was not linked to overall survival or disease-free survival. Patients whose IHC-positive lymph nodes were in the N2 position had statistically significantly worse survival rates (HR, 2.04; P = .017).

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Real-time reverse transcriptase-PCR was used to analyze lymph nodes from 256 patients: 176 (69%) were PCR-positive (52% in N1 position; 48% in N2 position). PCR-positivity was not associated with overall survival or disease-free survival.


  1. Martin LW, D’Cunha J, Wang X, et al. Detection of occult micrometastases in patients with clinical stage I non-small-cell lung cancer: a prospective analysis of mature results of CALGB 9761 (Alliance) [published online ahead of print February 29, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.63.4543.