Detection of MAGE-A transcripts in bone marrow is an independent prognostic factor in operable non-small-cell lung cancer

Clin Cancer Res. 2007 Jul 1;13(13):3840-7. doi: 10.1158/1078-0432.CCR-06-2507.

Abstract

Purpose: MAGE-A gene expression in humans is mostly restricted to tumor cells, and the role of MAGE-A transcripts and peptides as diagnostic markers and therapeutic targets is currently under investigation. Thus far, the clinical relevance of MAGE-A transcripts as marker for disseminated tumor cells in bone marrow of patients with operable lung cancer without overt metastases is still unclear.

Experimental design: Preoperative bone marrow aspirates from 50 consecutive patients with operable non-small-cell lung cancer free of distant metastases (i.e., pT(1-4) pN(0-2) M(0) R(0)) were admitted to the study. Each bone marrow sample was divided and examined using multimarker MAGE-A reverse transcription-PCR (RT-PCR) and immunocytochemical staining with the anti-pancytokeratin antibody A45-B/B3. Multimarker MAGE-A RT-PCR consisted of multiple subtype-specific nested RT-PCRs with primers for MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12. The median follow-up duration was 92 months (range, 18-110 months).

Results: Twenty-six (52%) lung cancer patients harbored MAGE-A transcripts in their bone marrow, as opposed to none of the 30 healthy controls tested. In all 7 patients with immunocytochemically positive bone marrow, MAGE-A transcripts were also detected. All different MAGE-A subtypes (MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12) were observed. Sixty-five percent of patients with MAGE-A transcripts in bone marrow exhibited only one subtype. Univariate (P = 0.03, log-rank-test) and multivariate survival analysis showed that MAGE-A transcripts in bone marrow were associated with poor outcome in pN(0) patients (P = 0.02; relative risk, 7.6).

Conclusions: Detection of MAGE-A transcripts in bone marrow predicts an unfavorable outcome in patients with early-stage operable lung cancer. This finding indicates that MAGE-A transcripts are clinically relevant markers of micrometastatic spread in lung cancer and supports further investigation of MAGE-A as potential future therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm
  • Bone Marrow Cells / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Male
  • Melanoma-Specific Antigens
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, Neoplasm
  • Melanoma-Specific Antigens
  • Neoplasm Proteins