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

Lung Cancer. 2010 Mar;67(3):290-5. doi: 10.1016/j.lungcan.2009.04.012. Epub 2009 May 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Female
  • Humans
  • Immunotherapy
  • Keratin-19 / genetics
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Melanoma-Specific Antigens
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Patient Selection*
  • RNA, Neoplasm / analysis
  • RNA, Neoplasm / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*

Substances

  • Antigens, Neoplasm
  • Keratin-19
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • RNA, Neoplasm