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A high tumour-stroma ratio (TSR) in colon tumours and its metastatic lymph nodes predicts poor cancer-free survival and chemo resistance

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Abstract

Purpose

Despite known high-risk features, accurate identification of patients at high risk of cancer recurrence in colon cancer remains a challenge. As tumour stroma plays an important role in tumour invasion and metastasis, the easy, low-cost and highly reproducible tumour-stroma ratio (TSR) could be a valuable prognostic marker, which is also believed to predict chemo resistance.

Methods

Two independent series of patients with colon cancer were selected. TSR was estimated by microscopic analysis of 4 µm haematoxylin and eosin (H&E) stained tissue sections of the primary tumour and the corresponding metastatic lymph nodes. Patients were categorized as TSR-low (≤ 50%) or TSR-high (> 50%). Differences in overall survival and cancer-free survival were analysed by Kaplan–Meier curves and cox-regression analyses. Analyses were conducted for TNM-stage I–II, TNM-stage III and patients with an indication for chemotherapy separately.

Results

We found that high TSR was associated with poor cancer-free survival in TNM-stage I–II colon cancer in two independent series, independent of other known high-risk features. This association was also found in TNM-stage III tumours, with an additional prognostic value of TSR in lymph node metastasis to TSR in the primary tumour alone. In addition, high TSR was found to predict chemo resistance in patients receiving adjuvant chemotherapy after surgical resection of a TNM-stage II–III colon tumour.

Conclusion

In colon cancer, the TSR of both primary tumour and lymph node metastasis adds significant prognostic value to current pathologic and clinical features used for the identification of patients at high risk of cancer recurrence, and also predicts chemo resistance.

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Data availability

Data and material cannot be shared publicly because of ethical concerns. Patients were included on a no objection base to conduct retrospective data studies and publish findings, but were not asked for permission to publish full encrypted data. Data are available from the VieCuri Institutional Data Access (contact via wetenschapsbureau@viecuri.nl) for researchers who meet the criteria for access to confidential data.

Code availability

Codes are available upon request via corresponding author.

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Funding

The authors received no specific funding for this work.

Author information

Authors and Affiliations

  1. Department of Surgery, VieCuri Medical Centre, Tegelseweg 210, 5912 BL, Venlo, The Netherlands

    M. T. A. Strous & F. J. Vogelaar

  2. Department of Epidemiology, GROW School for Oncology and Developmental Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands

    M. T. A. Strous & M. L. G. Janssen-Heijnen

  3. Department of Pathology, VieCuri Medical Centre, Venlo, The Netherlands

    T. K. E. Faes, A. L. H. M. Gubbels & A. P. de Bruïne

  4. Department of Surgery, Jeroen Bosch Hospital, ’s-Hertogenbosch, The Netherlands

    R. L. A. van der Linden & K. Bosscha

  5. Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands

    W. E. Mesker

  6. Department of Pathology, Jeroen Bosch Hospital, ’s-Hertogenbosch, The Netherlands

    C. M. Bronkhorst

  7. Department of Epidemiology, VieCuri Medical Center, Venlo, The Netherlands

    M. L. G. Janssen-Heijnen

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  1. M. T. A. Strous
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Contributions

Conceptualization: MTAS, FJV. Data curation: MTAS, TKEF, AHLMG, RLAvdL, FJV. Formal analysis: MTAS. Investigation: MTAS, TKEF, AHLMG, APdB. Methodology: MTAS, MLGJ-H. Project administration: MTAS, FJV. Resources: MTAS, RLAvdL, WEM, KB, CMB, FJV, APdB. Supervision: MLGJ-H, FJV, APdB. Validation: MTAS, RLAvdL, WEM. Visualization: MTAS. Writing—original draft: MTAS. Writing—review and editing: TKEF, RLAvdL, WEM, KB, CMB, MLGJ-H, FJV, APdB.

Corresponding author

Correspondence to M. T. A. Strous.

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Conflict of interest

The authors have declared that no competing interest exists.

Ethical approval (Research involving human participants and/or animals)

This study was approved by the research committee and the Board of Directors of VieCuri Medical Centre and Jeroen Bosch Hospital. Data were obtained under the law ‘scientific research and statistics in the interest of public health, where asking for permission is not possible or appropriate for several reasons’ in the Netherlands, unless patients objected to use of their personal medical record for scientific research. Data were encrypted with an encryption key provided by the NCR. Encryption was shortly lifted to access the patients’ number for accessing his/her medical record. Following extraction data were encrypted again. Prior collected material was reassessed. A waiver of informed consent was given by the METC Maastricht under the reference number 2020-1336.

Informed consent

Data were obtained under the law ‘scientific research and statistics in the interest of public health, where asking for permission is not possible or appropriate for several reasons’ in the Netherlands, unless patients objected to use of their personal medical record for scientific research.

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Strous, M.T.A., Faes, T.K.E., Gubbels, A.L.H.M. et al. A high tumour-stroma ratio (TSR) in colon tumours and its metastatic lymph nodes predicts poor cancer-free survival and chemo resistance. Clin Transl Oncol 24, 1047–1058 (2022). https://doi.org/10.1007/s12094-021-02746-y

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  • DOI: https://doi.org/10.1007/s12094-021-02746-y

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