Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma: Usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype

Shotaro Ono, Genichiro Ishii, Kanji Nagai, Teruhisa Takuwa, Junji Yoshida, Mitsuyo Nishimura, Tomoyuki Hishida, Keiju Aokage, Satoshi Fujii, Norihiko Ikeda, Atsushi Ochiai

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background: The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. Methods: A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. Results: Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells (P <.001). On the other hand, high podoplanin expression in the CAFs was also associated with a significantly poorer prognosis (P <.001). A multivariate analysis identified low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs as significantly independent prognostic factors for overall survival (P =.013 and P =.0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0% and showed a significantly poorer prognosis as compared with other groups (P <.001). Conclusions: The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.

Original languageEnglish
Pages (from-to)963-970
Number of pages8
JournalChest
Volume143
Issue number4
DOIs
Publication statusPublished - 2013
Externally publishedYes

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Squamous Cell Carcinoma
Cadherins
Phenotype
Lung
Neoplasms
Cancer-Associated Fibroblasts
Tumor Microenvironment
Survival
Multivariate Analysis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma : Usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype. / Ono, Shotaro; Ishii, Genichiro; Nagai, Kanji; Takuwa, Teruhisa; Yoshida, Junji; Nishimura, Mitsuyo; Hishida, Tomoyuki; Aokage, Keiju; Fujii, Satoshi; Ikeda, Norihiko; Ochiai, Atsushi.

In: Chest, Vol. 143, No. 4, 2013, p. 963-970.

Research output: Contribution to journalArticle

Ono, Shotaro ; Ishii, Genichiro ; Nagai, Kanji ; Takuwa, Teruhisa ; Yoshida, Junji ; Nishimura, Mitsuyo ; Hishida, Tomoyuki ; Aokage, Keiju ; Fujii, Satoshi ; Ikeda, Norihiko ; Ochiai, Atsushi. / Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma : Usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype. In: Chest. 2013 ; Vol. 143, No. 4. pp. 963-970.
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title = "Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma: Usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype",
abstract = "Background: The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. Methods: A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. Results: Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells (P <.001). On the other hand, high podoplanin expression in the CAFs was also associated with a significantly poorer prognosis (P <.001). A multivariate analysis identified low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs as significantly independent prognostic factors for overall survival (P =.013 and P =.0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0{\%} and showed a significantly poorer prognosis as compared with other groups (P <.001). Conclusions: The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.",
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TY - JOUR

T1 - Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma

T2 - Usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype

AU - Ono, Shotaro

AU - Ishii, Genichiro

AU - Nagai, Kanji

AU - Takuwa, Teruhisa

AU - Yoshida, Junji

AU - Nishimura, Mitsuyo

AU - Hishida, Tomoyuki

AU - Aokage, Keiju

AU - Fujii, Satoshi

AU - Ikeda, Norihiko

AU - Ochiai, Atsushi

PY - 2013

Y1 - 2013

N2 - Background: The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. Methods: A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. Results: Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells (P <.001). On the other hand, high podoplanin expression in the CAFs was also associated with a significantly poorer prognosis (P <.001). A multivariate analysis identified low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs as significantly independent prognostic factors for overall survival (P =.013 and P =.0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0% and showed a significantly poorer prognosis as compared with other groups (P <.001). Conclusions: The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.

AB - Background: The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. Methods: A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. Results: Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells (P <.001). On the other hand, high podoplanin expression in the CAFs was also associated with a significantly poorer prognosis (P <.001). A multivariate analysis identified low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs as significantly independent prognostic factors for overall survival (P =.013 and P =.0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0% and showed a significantly poorer prognosis as compared with other groups (P <.001). Conclusions: The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.

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U2 - 10.1378/chest.12-0913

DO - 10.1378/chest.12-0913

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