Abstract 343: Molecular markers for detection of micrometastases in regional lymph nodes from patients undergoing surgery for non-small cell lung cancer

Abstract

Abstract PURPOSE: Lung cancer retains its status as the most common cancer in the world, with an estimated 1.5 million cases diagnosed in 2007, accounting for about 12% of all cancers. Identifying microscopic lynph-node metastases, could have clinical importance in selecting patients for adjuvant treatment. The purpose of this study wasis to Iidentify and evaluate molecular markers for detection of micrometastases in regional lymph nodes from patients undergoing surgery for non-small cell lung cancer. PATIENTS AND METHODS: Candidate micrometasis markers were selected based on digital transcript profiling in EST and SAGE databases, searching for transcripts with high levels in lung cancers and very low levels in normal lymph nodes. Surfactant protein C (SFTPC) and cytokeratin 19 (CK19) mRNA levels in tumor biopsies and resected regional lymp nodes (N=38) from 24 patients undergoing surgery for non-small cell lung cancer were measured by quantitative RT-PCR. A control material consisting of 22 normal mesenterial lymph nodes from patients undergoing surgery for benign colon disorders was analyzed in parallell. RESULTS: The median relative CK19SFTPC mRNA level in the non-small cell lung tumor biopsies were 446 times higher than the highest level in normal control lymph nodes. SFTPC mRNA was not detectable in the normal lymph nodes, whereas the tumor levels were high (Cq-values ranging from 17-25). Using the highest CK19 mRNA level in the normal lymph nodes as a cut-off, four out of five (80%) lymph nodes from patients with known lymph node metastases (by routine histology) had elevated CK19 levels. Accordingly, 5 (15%) of 33 lymph nodes from patients without known metastases (node-negative) had elevated levels of CK19 mRNA. SFTPC mRNA were detectable in 31 of the 33 lymph nodes from node-negative patients, although the median relative level was 7.1 times higher in the 5 lymph nodes from node-positive patients (P=0.002, Mann-Witney test). Elevated CK19 and SFTPC mRNA levels in regional lymph nodes without known metastases may reflect the presence of micrometastases. CONCLUSION: SFTPC and CK19 mRNA are promising surrogate markers for detection of micrometastases in regional lymph nodes from non-small cell lung cancer patients. However, clinical follow-up in a larger cohort is needed to eludicate the prognostic value of such findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 343. doi:10.1158/1538-7445.AM2011-343