The difference in Ezrin–pAkt signaling axis between lepidic and papillary predominant invasive adenocarcinomas of the lung

Kazunori Hata, Junji Yoshida, Hibiki Udagawa, Hiroko Hashimoto, Satoshi Fujii, Tomoyuki Hishida, Takeshi Kuwata, Keiju Aokage, Motohiro Kojima, Atsushi Ochiai, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii

Research output: Contribution to journalArticle

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Abstract

Purpose: Histologic classification of invasive lung adenocarcinomas by predominant subtype has prognostic value. Papillary predominant adenocarcinoma (PPA) reportedly shows poorer prognosis than lepidic predominant adenocarcinoma (LPA); however, biological differences between PPA and LPA are unclear. The purpose of this study was to clarify biological differences between PPA and LPA. Methods: Clinicopathological characteristics of invasive 62 PPAs and 117 LPAs smaller than 30 mm were investigated. Furthermore, we compared immunochemical staining scores of 9 molecular markers (E-cadherin, S100A4, fibronectin, integrinβ1, ezrin, GLUT1, ALDH1, SOX2 and Nanog) between PPA and LPA. We performed Western blot analysis using ezrin shRNA-knockdown lung adenocarcinoma cell lines to examine whether molecules that are highly expressed in PPA, such as ezrin, affect pAkt. Finally, we performed immunochemical staining to compare pAkt expression level in PPA and LPA. Results: Lymphovascular and pleural invasion and lymph node metastasis were significantly more often detected in PPA than in LPA (lymphatic permeation: 31 vs 3 %, vascular invasion: 35 vs 3 %, pleural invasion: 29 vs 5 %, lymph node metastasis: 18 vs 1 %; all P < 0.01). Immunohistochemical (IHC) study revealed that expression score of ezrin was significantly higher in PPA than in LPA (38.3 vs 15.0; P < 0.01). The level of pAkt decreased in shEzrin-induced PC-9 and A549 cancer cells. Moreover, the IHC staining score of pAkt was significantly higher in PPA than in LPA (13.3 vs 0.0; P < 0.01). Conclusions: Our results show that the activation of the ezrin–pAkt signaling axis is associated with the more aggressive clinicopathological features of PPA compared with LPA.

Original languageEnglish
Pages (from-to)1421-1430
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume142
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1
Externally publishedYes

Fingerprint

Papillary Adenocarcinoma
Adenocarcinoma
Staining and Labeling
Lymph Nodes
Adenocarcinoma of lung
Neoplasm Metastasis
Cadherins
Fibronectins
Small Interfering RNA
Blood Vessels
Western Blotting

Keywords

  • Ezrin
  • Lepidic predominant adenocarcinoma
  • Lung adenocarcinoma
  • pAkt
  • Papillary predominant adenocarcinoma
  • Predominant subtype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The difference in Ezrin–pAkt signaling axis between lepidic and papillary predominant invasive adenocarcinomas of the lung. / Hata, Kazunori; Yoshida, Junji; Udagawa, Hibiki; Hashimoto, Hiroko; Fujii, Satoshi; Hishida, Tomoyuki; Kuwata, Takeshi; Aokage, Keiju; Kojima, Motohiro; Ochiai, Atsushi; Suzuki, Kenji; Tsuboi, Masahiro; Ishii, Genichiro.

In: Journal of Cancer Research and Clinical Oncology, Vol. 142, No. 7, 01.07.2016, p. 1421-1430.

Research output: Contribution to journalArticle

Hata, K, Yoshida, J, Udagawa, H, Hashimoto, H, Fujii, S, Hishida, T, Kuwata, T, Aokage, K, Kojima, M, Ochiai, A, Suzuki, K, Tsuboi, M & Ishii, G 2016, 'The difference in Ezrin–pAkt signaling axis between lepidic and papillary predominant invasive adenocarcinomas of the lung', Journal of Cancer Research and Clinical Oncology, vol. 142, no. 7, pp. 1421-1430. https://doi.org/10.1007/s00432-016-2154-z
Hata, Kazunori ; Yoshida, Junji ; Udagawa, Hibiki ; Hashimoto, Hiroko ; Fujii, Satoshi ; Hishida, Tomoyuki ; Kuwata, Takeshi ; Aokage, Keiju ; Kojima, Motohiro ; Ochiai, Atsushi ; Suzuki, Kenji ; Tsuboi, Masahiro ; Ishii, Genichiro. / The difference in Ezrin–pAkt signaling axis between lepidic and papillary predominant invasive adenocarcinomas of the lung. In: Journal of Cancer Research and Clinical Oncology. 2016 ; Vol. 142, No. 7. pp. 1421-1430.
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abstract = "Purpose: Histologic classification of invasive lung adenocarcinomas by predominant subtype has prognostic value. Papillary predominant adenocarcinoma (PPA) reportedly shows poorer prognosis than lepidic predominant adenocarcinoma (LPA); however, biological differences between PPA and LPA are unclear. The purpose of this study was to clarify biological differences between PPA and LPA. Methods: Clinicopathological characteristics of invasive 62 PPAs and 117 LPAs smaller than 30 mm were investigated. Furthermore, we compared immunochemical staining scores of 9 molecular markers (E-cadherin, S100A4, fibronectin, integrinβ1, ezrin, GLUT1, ALDH1, SOX2 and Nanog) between PPA and LPA. We performed Western blot analysis using ezrin shRNA-knockdown lung adenocarcinoma cell lines to examine whether molecules that are highly expressed in PPA, such as ezrin, affect pAkt. Finally, we performed immunochemical staining to compare pAkt expression level in PPA and LPA. Results: Lymphovascular and pleural invasion and lymph node metastasis were significantly more often detected in PPA than in LPA (lymphatic permeation: 31 vs 3 {\%}, vascular invasion: 35 vs 3 {\%}, pleural invasion: 29 vs 5 {\%}, lymph node metastasis: 18 vs 1 {\%}; all P < 0.01). Immunohistochemical (IHC) study revealed that expression score of ezrin was significantly higher in PPA than in LPA (38.3 vs 15.0; P < 0.01). The level of pAkt decreased in shEzrin-induced PC-9 and A549 cancer cells. Moreover, the IHC staining score of pAkt was significantly higher in PPA than in LPA (13.3 vs 0.0; P < 0.01). Conclusions: Our results show that the activation of the ezrin–pAkt signaling axis is associated with the more aggressive clinicopathological features of PPA compared with LPA.",
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T1 - The difference in Ezrin–pAkt signaling axis between lepidic and papillary predominant invasive adenocarcinomas of the lung

AU - Hata, Kazunori

AU - Yoshida, Junji

AU - Udagawa, Hibiki

AU - Hashimoto, Hiroko

AU - Fujii, Satoshi

AU - Hishida, Tomoyuki

AU - Kuwata, Takeshi

AU - Aokage, Keiju

AU - Kojima, Motohiro

AU - Ochiai, Atsushi

AU - Suzuki, Kenji

AU - Tsuboi, Masahiro

AU - Ishii, Genichiro

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Purpose: Histologic classification of invasive lung adenocarcinomas by predominant subtype has prognostic value. Papillary predominant adenocarcinoma (PPA) reportedly shows poorer prognosis than lepidic predominant adenocarcinoma (LPA); however, biological differences between PPA and LPA are unclear. The purpose of this study was to clarify biological differences between PPA and LPA. Methods: Clinicopathological characteristics of invasive 62 PPAs and 117 LPAs smaller than 30 mm were investigated. Furthermore, we compared immunochemical staining scores of 9 molecular markers (E-cadherin, S100A4, fibronectin, integrinβ1, ezrin, GLUT1, ALDH1, SOX2 and Nanog) between PPA and LPA. We performed Western blot analysis using ezrin shRNA-knockdown lung adenocarcinoma cell lines to examine whether molecules that are highly expressed in PPA, such as ezrin, affect pAkt. Finally, we performed immunochemical staining to compare pAkt expression level in PPA and LPA. Results: Lymphovascular and pleural invasion and lymph node metastasis were significantly more often detected in PPA than in LPA (lymphatic permeation: 31 vs 3 %, vascular invasion: 35 vs 3 %, pleural invasion: 29 vs 5 %, lymph node metastasis: 18 vs 1 %; all P < 0.01). Immunohistochemical (IHC) study revealed that expression score of ezrin was significantly higher in PPA than in LPA (38.3 vs 15.0; P < 0.01). The level of pAkt decreased in shEzrin-induced PC-9 and A549 cancer cells. Moreover, the IHC staining score of pAkt was significantly higher in PPA than in LPA (13.3 vs 0.0; P < 0.01). Conclusions: Our results show that the activation of the ezrin–pAkt signaling axis is associated with the more aggressive clinicopathological features of PPA compared with LPA.

AB - Purpose: Histologic classification of invasive lung adenocarcinomas by predominant subtype has prognostic value. Papillary predominant adenocarcinoma (PPA) reportedly shows poorer prognosis than lepidic predominant adenocarcinoma (LPA); however, biological differences between PPA and LPA are unclear. The purpose of this study was to clarify biological differences between PPA and LPA. Methods: Clinicopathological characteristics of invasive 62 PPAs and 117 LPAs smaller than 30 mm were investigated. Furthermore, we compared immunochemical staining scores of 9 molecular markers (E-cadherin, S100A4, fibronectin, integrinβ1, ezrin, GLUT1, ALDH1, SOX2 and Nanog) between PPA and LPA. We performed Western blot analysis using ezrin shRNA-knockdown lung adenocarcinoma cell lines to examine whether molecules that are highly expressed in PPA, such as ezrin, affect pAkt. Finally, we performed immunochemical staining to compare pAkt expression level in PPA and LPA. Results: Lymphovascular and pleural invasion and lymph node metastasis were significantly more often detected in PPA than in LPA (lymphatic permeation: 31 vs 3 %, vascular invasion: 35 vs 3 %, pleural invasion: 29 vs 5 %, lymph node metastasis: 18 vs 1 %; all P < 0.01). Immunohistochemical (IHC) study revealed that expression score of ezrin was significantly higher in PPA than in LPA (38.3 vs 15.0; P < 0.01). The level of pAkt decreased in shEzrin-induced PC-9 and A549 cancer cells. Moreover, the IHC staining score of pAkt was significantly higher in PPA than in LPA (13.3 vs 0.0; P < 0.01). Conclusions: Our results show that the activation of the ezrin–pAkt signaling axis is associated with the more aggressive clinicopathological features of PPA compared with LPA.

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KW - Papillary predominant adenocarcinoma

KW - Predominant subtype

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