Expression of melanoma-antigen-A (MAGE-A) in disseminated tumor cells in regional lymph nodes of patients with operable non-small cell lung cancer.
OBJECTIVE
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.


METHODS
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.
Dango
Sebastian
S
Department of Thoracic Surgery, Albert-Ludwigs University Freiburg, 79106 Freiburg, Germany. sebastian.dango@uniklinik-freiburg.de
Wang
Xiao Tao
XT
Gold
Monika
M
Cucuruz
Beatrix
B
Klein
Christoph A
CA
Passlick
Bernward
B
Sienel
Wulf
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D053539:Keratin-19 / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D018579:Patient Selection; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; D053539:Keratin-19; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm