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Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung

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Immunohistochemical analysis for the identification of clinically relevant biomarkers is important. However, there have been no detailed reports about the heterogeneous expressions of the various markers in squamous cell carcinoma of the lung.


A total of 113 patients with squamous cell carcinoma of the lung with lymph node metastasis were included. The expression levels of 9 molecules (E-cadherin, S100A4, CD44, ALDH1, SOX2, EGFR, HER2, FGFR1 and VEGFR2) in the peripheral area and central area of primary tumor and metastatic lymph nodes were evaluated by immunohistochemistry. The differences in the staining scores of these molecules among the three areas were assessed. We also analyzed the relationships between the expression levels of these molecules and the recurrence-free survival.


The E-cadherin expression was higher in the central area than in the peripheral area and metastatic lymph nodes (median staining score: 60 vs. 50, 30); the CD44 expression was higher in the central area than in the metastatic lymph nodes (117 vs. 90); and the EGFR expression was higher in the central area than in the peripheral area and metastatic lymph nodes (163 vs. 130, 110). Low CD44 expression in the central area, low EGFR expression in the peripheral area and high SOX2 expression in the metastatic lymph nodes were associated with a shorter recurrence-free survival (p < 0.01, p = 0.02, p = 0.03, respectively).


Our findings confirmed that some molecular markers exhibited different expression levels in anatomically different areas and suggested that area-by-area immunohistochemical analysis for biomarkers may provide useful information for more precise prediction of the recurrence.

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We thank Yuka Nakamura for her help with the immunohistochemical analyses in this study. This work was supported by the National Cancer Center Research and Development Fund (23-A-12), Foundation for the Promotion of Cancer Research, 3rd Term Comprehensive 10-Year Strategy for Cancer Control, Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, and JSPS KAKENHI (24659185).

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The authors have no conflict of interests to disclose.

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Correspondence to Genichiro Ishii.

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Udagawa, H., Ishii, G., Morise, M. et al. Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung. J Cancer Res Clin Oncol 141, 1417–1425 (2015). https://doi.org/10.1007/s00432-015-1912-7

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  • Squamous cell carcinoma
  • Lung cancer
  • Immunohistochemistry
  • Heterogeneity
  • Postoperative prognosis