Expression of melanoma-antigen-A (MAGE-A) in disseminated tumor cells in regional lymph nodes of patients with operable non-small cell lung cancer☆
Received 23 October 2008; received in revised form 9 March 2009; accepted 20 April 2009. published online 21 May 2009.
Abstract
Purpose
Single disseminated tumor cells are detectable in regional lymph nodes of 30–50% patients with early-stage non-small cell lung cancer (NSCLC). This study investigated if these disseminated tumor cells express MAGE-A and thus might be targeted by adjuvant anti-MAGE-A immunotherapies.
Experimental design
Lymph nodes of 32 consecutive patients without neoadjuvant therapy were removed by systematic lymphadenectomy during resection of NSCLC. One-hundred of these lymph nodes were cut into two equal halves which were examined using either routine histo-pathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT-PCR amplification of cytokeratin 19 transcripts was applied for the detection of disseminated tumor cells. Expression of MAGE-A was analyzed using one single primer pair amplifying subgroups MAGE-A1 to -A6 in one qRT-PCR reaction.
Results
Ninety-four (94%) lymph nodes were tumor-free by histo-pathology. qRT-PCR detected disseminated tumor cells in 26 (28%) of these lymph nodes resulting in 19 (59%) patients with disseminated tumor cells. All of the remaining 6 lymph nodes that were judged by the pathologist to contain tumor cells exhibited CK19 transcripts. Fifteen (46%) lymph nodes with disseminated tumor cells contained MAGE-A transcripts resulting in 12 (37%) patients with disseminated tumor cells which expressed MAGE-A. There was no correlation between clinico-pathological parameters and the occurrence of disseminated tumor cells or their MAGE-A expression.
Conclusions
Since 37% of patients with operable NSCLC harbored disseminated tumor cells that expressed MAGE-A, only these patients might benefit from adjuvant immunotherapies directed against MAGE-A1 to -A6. This study may provide a basis for the preselection of patients to be included in such immunotherapy trials after resection of NSCLC.
ABSTRACT