Skip to main content
Top
Published in: International Journal of Colorectal Disease 12/2021

Open Access 01-12-2021 | Colon Cancer | Original Article

Tumour-stroma ratio outperforms tumour budding as biomarker in colon cancer: a cohort study

Authors: Marloes A. Smit, Gabi W. van Pelt, Valeska Terpstra, Hein Putter, Rob A. E. M. Tollenaar, Wilma E. Mesker, J. Han J. M. van Krieken

Published in: International Journal of Colorectal Disease | Issue 12/2021

Login to get access

Abstract

The tumour-stroma ratio (TSR) and tumour budding (TB) are two high-risk factors with potential to be implemented in the next TNM classification. The aim of the current study was to evaluate the practical application of the two biomarkers based on reproducibility, independency and prognostic value. Patients diagnosed with stage II or III colon cancer who underwent surgery between 2005 and 2016 were included. Both TSR and TB were scored on haematoxylin and eosin-stained tissue sections. The TSR, based on the relative amount of stroma, was scored in increments of 10%. TB was scored following the consensus guidelines; a bud was defined as ≤ 4 tumour cells. For analysis, three categories were used. Cohen’s kappa was used for reproducibility. The prognostic value was determined with survival analysis. In total, 246 patients were included. The TSR distribution was N = 137 (56%) stroma-low and N = 109 (44%) stroma-high. The TB distribution was TB-low N = 194 (79%), TB-intermediate N = 35 (14%) and TB-high N = 17 (7%). The reproducibility of the TSR was good (interobserver agreement kappa = 0.83 and intraobserver agreement kappa = 0.82), whereas the inter- and intraobserver agreement for scoring TB was moderate (kappa 0.47 and 0.45, respectively). The survival analysis showed an independent prognostic value for disease-free survival for TSR (HR 1.57; 95% CI 1.01–2.44; p = 0.048) and for TB-high (HR 2.01; 95% CI 1.02–3.96; p = 0.043). Based on current results, we suggest the TSR is a more reliable parameter in daily practice due to better reproducibility and independent prognostic value for disease-free survival.
Appendix
Available only for authorised users
Literature
1.
go back to reference Aldecoa I, Atares B, Tarragona J, Bernet L, Sardon JD, Pereda T, Villar C, Mendez MC, Gonzalez-Obeso E, Elorriaga K, Alonso GL, Zamora J, Planell N, Palacios J, Castells A, Matias-Guiu X, Cuatrecasas M (2016) Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study. Virchows Arch 469:385–394. https://doi.org/10.1007/s00428-016-1990-1CrossRefPubMedPubMedCentral Aldecoa I, Atares B, Tarragona J, Bernet L, Sardon JD, Pereda T, Villar C, Mendez MC, Gonzalez-Obeso E, Elorriaga K, Alonso GL, Zamora J, Planell N, Palacios J, Castells A, Matias-Guiu X, Cuatrecasas M (2016) Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study. Virchows Arch 469:385–394. https://​doi.​org/​10.​1007/​s00428-016-1990-1CrossRefPubMedPubMedCentral
3.
go back to reference Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E, Brouwers M, Charette M, Haller DG (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408–3419. https://doi.org/10.1200/JCO.2004.05.063CrossRefPubMed Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E, Brouwers M, Charette M, Haller DG (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408–3419. https://​doi.​org/​10.​1200/​JCO.​2004.​05.​063CrossRefPubMed
5.
go back to reference Croner RS, Geppert CI, Bader FG, Nitsche U, Spath C, Rosenberg R, Zettl A, Matias-Guiu X, Tarragona J, Guller U, Sturzl M, Zuber M (2014) Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, Multicentre study. Br J Cancer 110:2544–2550. https://doi.org/10.1038/bjc.2014.170CrossRefPubMedPubMedCentral Croner RS, Geppert CI, Bader FG, Nitsche U, Spath C, Rosenberg R, Zettl A, Matias-Guiu X, Tarragona J, Guller U, Sturzl M, Zuber M (2014) Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, Multicentre study. Br J Cancer 110:2544–2550. https://​doi.​org/​10.​1038/​bjc.​2014.​170CrossRefPubMedPubMedCentral
8.
go back to reference Dekker JW, Gooiker GA, Bastiaannet E, van den Broek CB, van der Geest LG, van de Velde CJ, Tollenaar RA, Liefers GJ. Steering Committee of the 'Quality Information System Colorectal Cancer P (2014) Cause of death the first year after curative colorectal cancer surgery; a prolonged impact of the surgery in elderly colorectal cancer patients. Eur J Surg Oncol 40:1481–1487. https://doi.org/10.1016/j.ejso.2014.05.010 Dekker JW, Gooiker GA, Bastiaannet E, van den Broek CB, van der Geest LG, van de Velde CJ, Tollenaar RA, Liefers GJ. Steering Committee of the 'Quality Information System Colorectal Cancer P (2014) Cause of death the first year after curative colorectal cancer surgery; a prolonged impact of the surgery in elderly colorectal cancer patients. Eur J Surg Oncol 40:1481–1487. https://​doi.​org/​10.​1016/​j.​ejso.​2014.​05.​010
12.
13.
go back to reference Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa EMF, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:1350–1356. https://doi.org/10.1038/nm.3967CrossRefPubMedPubMedCentral Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa EMF, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:1350–1356. https://​doi.​org/​10.​1038/​nm.​3967CrossRefPubMedPubMedCentral
15.
go back to reference Huijbers A, Tollenaar RA, Pelt GW, Zeestraten EC, Dutton S, McConkey CC, Domingo E, Smit VT, Midgley R, Warren BF, Johnstone EC, Kerr DJ, Mesker WE (2013) The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol 24:179–185. https://doi.org/10.1093/annonc/mds246CrossRefPubMed Huijbers A, Tollenaar RA, Pelt GW, Zeestraten EC, Dutton S, McConkey CC, Domingo E, Smit VT, Midgley R, Warren BF, Johnstone EC, Kerr DJ, Mesker WE (2013) The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol 24:179–185. https://​doi.​org/​10.​1093/​annonc/​mds246CrossRefPubMed
16.
go back to reference Koelzer VH, Assarzadegan N, Dawson H, Mitrovic B, Grin A, Messenger DE, Kirsch R, Riddell RH, Lugli A, Zlobec I (2017) Cytokeratin-based assessment of tumour budding in colorectal cancer: analysis in stage II patients and prospective diagnostic experience J Pathol. Clin Res 3:171–178. https://doi.org/10.1002/cjp2.73CrossRef Koelzer VH, Assarzadegan N, Dawson H, Mitrovic B, Grin A, Messenger DE, Kirsch R, Riddell RH, Lugli A, Zlobec I (2017) Cytokeratin-based assessment of tumour budding in colorectal cancer: analysis in stage II patients and prospective diagnostic experience J Pathol. Clin Res 3:171–178. https://​doi.​org/​10.​1002/​cjp2.​73CrossRef
17.
20.
go back to reference Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, El Zimaity H, Flejou JF, Hansen TP, Hartmann A, Kakar S, Langner C, Nagtegaal I, Puppa G, Riddell R, Ristimaki A, Sheahan K, Smyrk T, Sugihara K, Terris B, Ueno H, Vieth M, Zlobec I (2016) Quirke P (2017) Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC). Mod Pathol 30:1299–1311. https://doi.org/10.1038/modpathol.2017.46CrossRef Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, El Zimaity H, Flejou JF, Hansen TP, Hartmann A, Kakar S, Langner C, Nagtegaal I, Puppa G, Riddell R, Ristimaki A, Sheahan K, Smyrk T, Sugihara K, Terris B, Ueno H, Vieth M, Zlobec I (2016) Quirke P (2017) Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC). Mod Pathol 30:1299–1311. https://​doi.​org/​10.​1038/​modpathol.​2017.​46CrossRef
22.
go back to reference Mesker WE, Junggeburt JM, Szuhai K, de Heer P, Morreau H, Tanke HJ, Tollenaar RA (2007) The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol 29:387–398PubMedPubMedCentral Mesker WE, Junggeburt JM, Szuhai K, de Heer P, Morreau H, Tanke HJ, Tollenaar RA (2007) The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol 29:387–398PubMedPubMedCentral
25.
26.
go back to reference Smit M vPG, Tollenaar R, Mesker W (2020) Uniform noting for international application of the tumour-stroma ratio as easy diagnostic tool (UNITED) study website. http://watchstroma.com/. Accessed 27 July 2020 Smit M vPG, Tollenaar R, Mesker W (2020) Uniform noting for international application of the tumour-stroma ratio as easy diagnostic tool (UNITED) study website. http://​watchstroma.​com/​. Accessed 27 July 2020
28.
go back to reference Vogelaar FJ, van Pelt GW, van Leeuwen AM, Willems JM, Tollenaar RA, Liefers GJ, Mesker WE (2016) Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study. Cell Oncol (Dordr) 39:537–544. https://doi.org/10.1007/s13402-016-0296-2CrossRef Vogelaar FJ, van Pelt GW, van Leeuwen AM, Willems JM, Tollenaar RA, Liefers GJ, Mesker WE (2016) Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study. Cell Oncol (Dordr) 39:537–544. https://​doi.​org/​10.​1007/​s13402-016-0296-2CrossRef
Metadata
Title
Tumour-stroma ratio outperforms tumour budding as biomarker in colon cancer: a cohort study
Authors
Marloes A. Smit
Gabi W. van Pelt
Valeska Terpstra
Hein Putter
Rob A. E. M. Tollenaar
Wilma E. Mesker
J. Han J. M. van Krieken
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Colorectal Disease / Issue 12/2021
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-021-04023-4

Other articles of this Issue 12/2021

International Journal of Colorectal Disease 12/2021 Go to the issue