Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer

Yonsei Med J. 2019 Nov;60(11):1005-1012. doi: 10.3349/ymj.2019.60.11.1005.


Purpose: Identification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield.

Materials and methods: In this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT).

Results: MRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively.

Conclusion: MRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.

Keywords: Aminoacyl tRNA synthetase; EBUS-TBNA; MRS; NSCLC; biomarker.

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / diagnosis*
  • Lymphatic Metastasis / pathology
  • Male
  • Methionine-tRNA Ligase / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • ROC Curve


  • Antigens, CD
  • Biomarkers, Tumor
  • Methionine-tRNA Ligase