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Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma

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Abstract

We previously reported that claspin is a key regulator in the progression of gastric cancer and renal cell carcinoma. However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by immunohistochemistry. In the non-neoplastic urothelium, the expression of claspin was either weak or absent, whereas UC tissues showed nuclear staining. The expression of claspin was detected in 58 (42%) of a total of 138 upper tract UC cases treated by radical nephroureterectomy without neoadjuvant chemotherapy. Claspin-positive UC cases were associated with nodular/flat morphology, variant histology, high tumor grade, high pathological T grade, and lymphatic and venous invasion. The expression of claspin was significantly associated with decreased progression-free survival and cancer-specific survival. In addition, claspin was co-expressed with Ki-67, PD-L1, HER2, EGFR, and p53 in consecutive tumor sections of UC. An immunohistochemical analysis of claspin in biopsy specimens revealed that strong to moderate claspin staining was more frequently observed in carcinoma in situ in comparison to dysplasia or the benign urothelium. Furthermore, immunocytochemistry for claspin on urine cytology slides demonstrated that the proportion of claspin-positive cells was significantly greater in high-grade UC than in benign cases. These results suggest that claspin may be a novel prognostic marker and a possible therapeutic target molecule for UC. Moreover, claspin could be a useful diagnostic biomarker of urothelial neoplasia.

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Acknowledgements

We thank Shinichi Norimura and Yuka Yamaguchi for the excellent technical assistance, and the Analysis Center of Life Science, Hiroshima University, for the use of its facilities.

Funding

This work was supported by Grants-in-Aid for Scientific Research (19K07434) from the Japan Society for the Promotion of Science. The Takeda Science Foundation also supported this work.

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Authors and Affiliations

  1. Department of Pathology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, Japan

    Go Kobayashi, Naohiro Uraoka & Naomi Sasaki

  2. Department of Urology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Tetsutaro Hayashi, Takashi Babasaki, Yohei Sekino, Shogo Inoue, Jun Teishima & Akio Matsubara

  3. Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Kazuhiro Sentani, Takashi Babasaki, Naohide Oue & Wataru Yasui

  4. Department of Urology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, Japan

    Masanori Hanamoto & Hiroyuki Nose

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  1. Go Kobayashi
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Contributions

Go Kobayashi: conceptualization, methodology, formal analysis, investigation, data curation, project administration, writing–original draft and writing-review and editing. Tetsutaro Hayashi: conceptualization, data curation, project administration, resources, and writing—review and editing. Kazuhiro Sentani: conceptualization, project administration, supervision, and writing—review and editing. Takashi Babasaki: conceptualization and writing—review and editing. Yohei Sekino: conceptualization and writing-review and editing. Shogo Inoue: conceptualization and writing—review and editing. Naohiro Uraoka: conceptualization and writing—review and editing. Masanori Hanamoto: conceptualization and writing-review and editing. Hiroyuki Nose: conceptualization and writing—review and editing. Jun Teishima: conceptualization and writing-review and editing. Naohide Oue: conceptualization and writing—review and editing. Akio Matsubara: conceptualization and writing—review and editing. Naomi Sasaki: conceptualization and writing—review and editing. Wataru Yasui: conceptualization and writing—review and editing. All authors reviewed and approved the final version.

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Kobayashi, G., Hayashi, T., Sentani, K. et al. Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma. Virchows Arch 480, 621–633 (2022). https://doi.org/10.1007/s00428-021-03239-7

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