Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung

Tetsuhiko Taira, Genichiro Ishii, Kanji Nagai, Kiyotaka Yoh, Yusuke Takahashi, Yuki Matsumura, Motohiro Kojima, Hironobu Ohmatsu, Koichi Goto, Seiji Niho, Hiroshi Takashima, Hiromasa Inoue, Yuichiro Ohe, Atsushi Ochiai

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28 Citations (Scopus)

Abstract

Tumor budding is morphologically defined as infiltration by small clusters of cancer cells. While the biological properties of budding cells in adenocarcinoma (decreased expression of adhesion molecules and of differentiation markers) have been elucidated, those of the cells in squamous cell carcinoma (SqCC) of the lung still remain to be clarified. We examined the clinicopathological data of 217 patients with SqCC of the lung. Furthermore we evaluated the immunohistochemical properties of the budding cells. Tumor budding was observed in 83 (38.2%) patients. A statistically significant difference was observed in overall 5-year survival rates between the cases showing tumor budding and the cases not showing budding (45.6% vs. 64.0%, p< 0.001). As compared with cancer cells forming solid nests, budding cells (BCs) exhibited reduced expression levels of the cellular adhesion molecules (E-cadherin; p= 0.004, β-catenin; p= 0.002) and increased expression levels of laminin-5γ2 (p= 0.001). On the other hand, no significant differences in the staining scores for differentiation markers (p63 and podoplanin) were found between BCs and cancer cells forming nests. Multivariate analysis revealed that tumor budding was a significant independent prognostic factor in patients with SqCC of the lung (p= 0.022). Tumor budding is an independent adverse prognostic factor in patients with SqCC of the lung. Although budding cells in SqCC exhibited reduced expression levels of the cellular adhesion molecules, the expression levels of specific differentiation markers were retained, suggesting that the budding mechanism in SqCC may differ, at least in part, from that in adenocarcinoma.

Original languageEnglish
Pages (from-to)423-430
Number of pages8
JournalLung Cancer
Volume76
Issue number3
DOIs
Publication statusPublished - 2012 Jun 1

Keywords

  • Epithelial Mesenchymal Transition (EMT)
  • Lung cancer
  • Prognostic factor
  • Squamous cell carcinoma
  • Tumor budding

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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  • Cite this

    Taira, T., Ishii, G., Nagai, K., Yoh, K., Takahashi, Y., Matsumura, Y., Kojima, M., Ohmatsu, H., Goto, K., Niho, S., Takashima, H., Inoue, H., Ohe, Y., & Ochiai, A. (2012). Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung. Lung Cancer, 76(3), 423-430. https://doi.org/10.1016/j.lungcan.2011.11.010