Gene diagnosis of micrometastases in regional lymph nodes of patients with stage I non-small cell lung cancer: impact on staging and prognosis

Abstract

The long-term survival of patients with completely resected stage I non-small cell lung cancer (NSCLC) is not optimal because of undetected lymph node micrometastasis at the time of surgery. The aim of this study is to evaluate the role of survivin and livin mRNA expression in histopathologically negative lymph nodes of stage I NSCLC patients as markers of micrometastasis. Clinical data and tissue samples of primary tumor and lymph nodes were collected from 44 patients with stage I NSCLC. Reverse-transcriptase-PCR (RT-PCR) was used to detect survivin and livin mRNA expression in these tumor and lymph node samples. Survivin mRNA was detected in all tumors, and livin mRNA was detectable in 39 of the 44 primary tumors. The cut-off values of survivin and livin mRNA levels for diagnosing micrometastasis in lymph nodes were set up according to the expression of survivin and livin mRNA in control lymph nodes. Fifteen (34.1 %) of 44 stage I NSCCL patients had micrometastasis in lymph nodes by survivin and/or livin mRNA positive expression. Survival analysis showed higher rate of cancer recurrences and tumor-related death in patients with lymph node micrometastasis (P < 0.001 and P = 0.001, respectively). Tumor-free survival and overall survival were significantly worse in patients with lymph node micrometastasis compared with those without such micrometastasis (P = 0.007 and P = 0.01, respectively). RT-RCR assay for survivin and livin mRNA can be considered as useful diagnostic tool for the detection of lymph node micrometastasis for stage I NSCLC patients.