Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

INTRODUCTION: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC). METHODS: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data. RESULTS: All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004). CONCLUSIONS: Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.