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STAT3 activation in thymic epithelial tumors: correlation with cyclin D1, JAK3, and clinical behavior

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General Thoracic and Cardiovascular Surgery Aims and scope Submit manuscript

Abstract

Objectives

Thymic epithelial tumors are the most common adult mediastinal tumors; however, their growth mechanism remains relatively unknown. Among the JAK/STAT pathway-related proteins, which control various intracellular events, STAT3 is deeply involved in cell proliferation. Constitutive activation of STAT3 and the resulting overexpression of cyclin D1 have been confirmed in various tumors, but have not been thoroughly investigated in thymic epithelial tumors. In this study, we immunohistochemically examined STAT3 activation, cyclin D1 expression, and JAK3 activation in thymic epithelial tumors and statistically analyzed their correlation with clinicopathological features.

Methods

Formalin-fixed paraffin-embedded specimens of 94 thymic epithelial tumors surgically resected at Kyorin University Hospital between 2005 and 2018 were included in this study. pSTAT3, cyclin D1, and pJAK3 were immunohistochemically examined, and the correlation with histology, Masaoka stage, and survival time was statistically analyzed.

Results

Cyclin D1 was found to be significantly overexpressed in the STAT3-activated group. This phenomenon was associated with histology and Masaoka stage. JAK3 was also activated in thymic epithelial tumors; however, JAK3 and STAT3 activation were not always correlated. Using survival time analysis, the STAT3-activated group, cyclin D1-expressed group, and JAK3-activated group had significantly lower progression-free survival times than those for both the non-activated and non-expressed groups.

Conclusions

STAT3 activation may promote cyclin D1 overexpression in thymic epithelial tumors, and intracellular signaling pathways other than JAK3 may be involved in STAT3 activation. STAT3 activation, cyclin D1 overexpression, and JAK3 activation are biomarker candidates that indicate clinically poor prognosis.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This study was funded by JSPS KAKENHI (Grant Number JP20K07451).

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Authors and Affiliations

  1. Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Naota Okabe, Masachika Fujiwara & Hiroshi Kamma

  2. Department of Thoracic Surgery and Thyroid Surgery, Kyorin University School of Medicine, Mitaka, 181-8611, Japan

    Keisei Tachibana, Ryota Tanaka & Haruhiko Kondo

Authors
  1. Naota Okabe
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  2. Masachika Fujiwara
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  3. Keisei Tachibana
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  6. Hiroshi Kamma
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Correspondence to Masachika Fujiwara.

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Okabe, N., Fujiwara, M., Tachibana, K. et al. STAT3 activation in thymic epithelial tumors: correlation with cyclin D1, JAK3, and clinical behavior. Gen Thorac Cardiovasc Surg 69, 1482–1491 (2021). https://doi.org/10.1007/s11748-021-01655-9

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  • DOI: https://doi.org/10.1007/s11748-021-01655-9

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