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Prognostic significance of combining immunohistochemical markers for cancer-associated fibroblasts in lung adenocarcinoma tissue

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Abstract

Cancer-associated fibroblasts (CAFs), activated fibroblasts in a cancer microenvironment, exert various effects upon carcinoma cells including lung adenocarcinoma cells. Various markers identifying CAFs have been proposed, but the correlations among these markers proposed and their clinicopathological significance have remained largely unknown. Therefore, in this study, we immunohistochemically evaluated the expression of alpha-smooth muscle actin (α-SMA), podoplanin, and periostin among these proposed markers in 92 cases of lung adenocarcinoma. These three markers were weakly correlated, but the relative abundance of α-SMA was significantly associated with high Ki-67 labelling index (LI), lymph node metastasis, and low 5-year overall survival (OS) rate of the patients. That of podoplanin was significantly associated with high pT and Ki-67 LI, distant metastasis, and low 5-year OS rate and that of periostin with high pT and Ki-67 LI. We then tentatively subclassified these cases into four groups according to high or low status of each of paired markers: α-SMA/podoplanin, α-SMA/periostin, and periostin/podoplanin. The α-SMA high/podoplanin high group was associated with the lowest survival rate (53.3%) among the four groups with significance. However, there were no significant differences in overall survival when the patients were classified according to the combinations of α-SMA/periostin or periostin/podoplanin. Results of our study firstly revealed the heterogeneity of CAFs in human lung adenocarcinoma tissue, and the analysis employing multiple markers of CAFs is generally required to study the clinical significance of CAFs in clinical materials.

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Acknowledgments

C.I. is supported by a scholarship from the Takeda Science Foundation (Osaka, Japan).

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Authors and Affiliations

  1. Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Chihiro Inoue, Ryoko Saito & Hironobu Sasano

  2. Tohoku University School of Medicine, Sendai, Miyagi, Japan

    Daisuke Tamatsuki

  3. Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University, Sendai, Miyagi, Japan

    Yasuhiro Miki

  4. Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

    Yoshinori Okada

Authors
  1. Chihiro Inoue
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  4. Ryoko Saito
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Contributions

C.I. and Y.M. designed the study and wrote the initial draft of the manuscript. C.I. and D.T. performed the experiments and analyzed the data. R.S. evaluated immunohistochemistry and supervised the interpretation of pathology. Y.O. collected tissue samples and supervised the interpretation of clinical data. H.S. supervised all experiments and edited the manuscript. All authors approved the submission of the final manuscript.

Corresponding author

Correspondence to Chihiro Inoue.

Ethics declarations

The protocol for this study was approved by the Ethics Committee at the Tohoku University School of Medicine (2018-193). This study has been performed in accordance with the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Inoue, C., Tamatsuki, D., Miki, Y. et al. Prognostic significance of combining immunohistochemical markers for cancer-associated fibroblasts in lung adenocarcinoma tissue. Virchows Arch 475, 181–189 (2019). https://doi.org/10.1007/s00428-019-02587-9

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  • DOI: https://doi.org/10.1007/s00428-019-02587-9

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