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Expression of cathepsins B, D and K in thymic epithelial tumours
  1. Naoko Yamaguchi1,2,
  2. Utano Tomaru1,
  3. Takayuki Kiuchi1,
  4. Akihiro Ishizu3,
  5. Takahiro Deguchi4,
  6. Noriyuki Otsuka1,
  7. Satoshi Tanaka5,
  8. Katsuji Marukawa4,6,
  9. Yoshihiro Matsuno4,
  10. Masanobu Kitagawa2,
  11. Masanori Kasahara1
  1. 1 Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  2. 2 Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  3. 3 Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan
  4. 4 Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
  5. 5 Center for Cause of Death Investigation, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  6. 6 Clinical Laboratory Science, School of Medical Technology, Health Sciences University of Hokkaido, Sapporo, Japan
  1. Correspondence to Dr Utano Tomaru, Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; tomaruu{at}


Aim Cathepsins are proteases that regulate a wide range of physiological processes, including protein turnover, cell signalling and antigen presentation. Recent studies have shown that cathepsins are highly upregulated in many types of tumours. Of the 15 cathepsins in humans, cathepsins V and S are abundantly expressed in the thymus, and we previously showed that the immunostaining of these cathepsins could serve as diagnostic markers for thymic epithelial tumours. However, little is known about the expression of other cathepsins in thymic epithelial tumours. To determine the diagnostic implications of cathepsins, we performed immunohistochemical analysis of cathepsin B (CTB), cathepsin D (CTD) and cathepsin K (CTK), all of which have been reported to correlate with the progression of squamous cell carcinoma.

Methods The association between cathepsin expression and clinicopathological features was evaluated in 122 cases of thymoma and thymic carcinoma.

Results CTB and CTD were frequently expressed in type A and type AB thymomas. In contrast, CTB and CTD were significantly less common in type B thymomas than in type A or AB thymomas. In type AB thymomas, the expression of CTB correlated with histological features, and was found predominantly in the type A component. Notably, CTK was expressed most commonly in thymic carcinomas, and patients who died of the disease showed increased expression of CTK.

Conclusions The expression of CTB and CTD correlated with the histological subtype of thymoma. In addition, the expression of CTK appears to be useful for the diagnosis of thymic carcinomas and as a prognostic marker.

  • histopathology
  • diagnosis
  • carcinoma
  • immunohistochemistry

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  • Handling editor Runjan Chetty.

  • Contributors NY and UT designed the study, analysed the data and wrote the manuscript. TK, AI, TD, NO, ST and KM analysed the data. YM analysed the data, supervised the research design and edited the manuscript. MKi and MKa reviewed and supervised the manuscript. All authors gave final approval for publication.

  • Funding This work was supported in part by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology of Japan (18H02629).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Medical Ethics Committee of Hokkaido University Hospital (approval number 015–0118).

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data availability statement Data are availableon reasonable request. The data and materials used in the current study are available from the corresponding author on reasonable request.