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Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ
  1. Michael Toss1,
  2. Islam Miligy1,
  3. Kylie Gorringe2,
  4. Karuna Mittal3,
  5. Ritu Aneja3,
  6. Ian Ellis1,
  7. Andrew Green1,
  8. Emad Rakha1
  1. 1 Histopathology, University of Nottingham School of Medicine, Nottingham, UK
  2. 2 Melbourne, Victoria, Australia
  3. 3 Atlanta, Georgia, USA
  1. Correspondence to Dr Michael Toss, Histopathology, University of Nottingham School of Medicine, Nottingham NG5 1PB, UK; msxms8{at}


Aims Cathepsin V (CTSV/CTSL2) is a lysosomal cysteine proteinase and plays a role in extracellular matrix degradation. It is associated with poor prognosis in invasive breast cancer (IBC), but its role in breast ductal carcinoma in situ (DCIS) remains unclear. In this study, we aimed to evaluate the prognostic significance of CTSV in DCIS.

Methods CTSV protein expression was immunohistochemically assessed in a well-characterised and annotated cohort of DCIS comprising pure DCIS (n=776) and DCIS coexisting with IBC (n=239). CTSV expression was analysed in tumour cells and surrounding stroma, including its association with clinicopathological parameters and outcome.

Results In pure DCIS, high CTSV expression was observed in 29% of epithelial tumour cells and 20% of surrounding stroma. High expression in both components was associated with features of poor prognosis including higher nuclear grade, hormone receptor negativity and HER2 positivity. In addition, stromal CTSV expression was associated with larger DCIS size, comedo-type necrosis and high proliferation index. DCIS associated with IBC showed higher CTSV expression than pure DCIS either within the epithelial tumour cells or surrounding stroma (p<0.0001 and p=0.001, respectively). In DCIS/IBC, CTSV expression was higher in the invasive component than DCIS component either in tumour cells or surrounding stroma (both p<0.0001). CTSV stromal expression was associated with invasive recurrence independent of other prognostic factors in patients treated with breast conserving surgery (HR=3.0, p=0.005).

Conclusion High expression of CTSV is associated with poor outcome in DCIS and is a potential marker to predict DCIS progression to invasive disease.

  • DCIS
  • proteolysis
  • CTSV
  • stroma
  • recurrence

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  • Handling editor Cheok Soon Lee.

  • Contributors All authors contributed to the design of the study, analysis of data and writing the manuscript.

  • Funding This research was supported and funded by the Egyptian Ministry of Higher Education and Scientific Research.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This article does not contain any studies with human participants or animals performed by any of the authors. This work obtained ethics approval to use the human tissue samples by the North West–Greater Manchester Central Research Ethics Committee under the title: Nottingham Health Science Biobank (NHSB) (reference number 15/NW/0685).

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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