Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma

Rie Matsuwaki, Genichiro Ishii, Yoshitaka Zenke, Shinya Neri, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Satoshi Fujii, Haruhiko Kondo, Tomoyuki Goya, Kanji Nagai, Atsushi Ochiai

Research output: Contribution to journalArticle

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Abstract

Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial-mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC. The aim of this study was to clarify predictive factor of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors.The immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC.

Original languageEnglish
Pages (from-to)905-911
Number of pages7
JournalCancer Science
Volume105
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Squamous Cell Carcinoma
Lymph Nodes
Recurrence
Lung
Neoplasms
Clusterin
Caveolins
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Cadherins
Cancer-Associated Fibroblasts
Multivariate Analysis

Keywords

  • Cancer-associated fibroblasts
  • Lung squamous cell carcinoma
  • Metastatic lymph node tumors
  • Recurrence
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma. / Matsuwaki, Rie; Ishii, Genichiro; Zenke, Yoshitaka; Neri, Shinya; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Fujii, Satoshi; Kondo, Haruhiko; Goya, Tomoyuki; Nagai, Kanji; Ochiai, Atsushi.

In: Cancer Science, Vol. 105, No. 7, 2014, p. 905-911.

Research output: Contribution to journalArticle

Matsuwaki, R, Ishii, G, Zenke, Y, Neri, S, Aokage, K, Hishida, T, Yoshida, J, Fujii, S, Kondo, H, Goya, T, Nagai, K & Ochiai, A 2014, 'Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma', Cancer Science, vol. 105, no. 7, pp. 905-911. https://doi.org/10.1111/cas.12434
Matsuwaki, Rie ; Ishii, Genichiro ; Zenke, Yoshitaka ; Neri, Shinya ; Aokage, Keiju ; Hishida, Tomoyuki ; Yoshida, Junji ; Fujii, Satoshi ; Kondo, Haruhiko ; Goya, Tomoyuki ; Nagai, Kanji ; Ochiai, Atsushi. / Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma. In: Cancer Science. 2014 ; Vol. 105, No. 7. pp. 905-911.
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abstract = "Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial-mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC. The aim of this study was to clarify predictive factor of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors.The immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC.",
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AU - Aokage, Keiju

AU - Hishida, Tomoyuki

AU - Yoshida, Junji

AU - Fujii, Satoshi

AU - Kondo, Haruhiko

AU - Goya, Tomoyuki

AU - Nagai, Kanji

AU - Ochiai, Atsushi

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AB - Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial-mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC. The aim of this study was to clarify predictive factor of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors.The immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC.

KW - Cancer-associated fibroblasts

KW - Lung squamous cell carcinoma

KW - Metastatic lymph node tumors

KW - Recurrence

KW - Tumor microenvironment

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