Tumour-stroma ratio has poor prognostic value in nonpedunculated T1 colorectal cancer: A multicentre case-cohort study.
T1 colorectal cancer
desmoplasia
prognosis
tumour microenvironment
tumour-stroma ratio
Journal
United European gastroenterology journal
ISSN: 2050-6414
Titre abrégé: United European Gastroenterol J
Pays: England
ID NLM: 101606807
Informations de publication
Date de publication:
10 Feb 2021
10 Feb 2021
Historique:
received:
10
09
2020
accepted:
28
10
2020
entrez:
10
2
2021
pubmed:
11
2
2021
medline:
11
2
2021
Statut:
aheadofprint
Résumé
Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer. Haematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up. All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p = 0.163). Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours.
Sections du résumé
BACKGROUND
BACKGROUND
Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer.
METHODS
METHODS
Haematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up.
RESULTS
RESULTS
All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p = 0.163).
CONCLUSIONS
CONCLUSIONS
Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours.
Identifiants
pubmed: 33566452
doi: 10.1177/2050640620975324
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.
Références
Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683-91.
Hashiguchi Y, Muro K, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25:1-42.
Antonelli G, Vanella G, Orlando D, et al. Recurrence and cancer-specific mortality after endoscopic resection of low- and high-risk pT1 colorectal cancers: a meta-analysis. Gastrointest Endosc. 2019;90:559-69.
Bosch SL, Teerenstra S, De Wilt JH, et al. Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions. Endoscopy. 2013;45:827-34.
Miyachi H, Kudo SE, Ichimasa K, et al. Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis. J Gastroenterol Hepatol. 2016;31:1126-32.
Van Pelt GW, Sandberg TP, Morreau H, et al. The tumour-stroma ratio in colon cancer: the biological role and its prognostic impact. Histopathology. 2018;73:197-206.
Courrech Staal EF, Wouters MW, Van Sandick JW, et al. The stromal part of adenocarcinomas of the oesophagus: does it conceal targets for therapy? Eur J Canc. 2010;46:720-8.
De Kruijf EM, Van Nes JG, Van De Velde CJ, et al. Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple- negative carcinoma patients. Breast Cancer Res Treat. 2011;125:687-96.
Dekker TJ, Van De Velde CJ, Van Pelt GW, et al. Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854). Breast Cancer Res Treat. 2013;139:371-9.
Wang K, Ma W, Wang J, et al. Tumor-stroma ratio is an independent predictor for survival in esophageal squamous cell carcinoma. J Thorac Oncol. 2012;7:1457-61.
Lv Z, Cai X, Weng X, et al. Tumor-stroma ratio is a prognostic factor for survival in hepatocellular carcinoma patients after liver resection or transplantation. Surgery. 2015;158:142-50.
Zhang T, Xu J, Shen H, et al. Tumor-stroma ratio is an independent predictor for survival in NSCLC. Int J Clin Exp Pathol. 2015;8:11348-55.
Mesker WE, Junggeburt JM, Szuhai K, et al. The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol. 2007;29:387-98.
Huijbers A, Tollenaar RA, Van Pelt GW, et al. The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol. 2013;24:179-85.
Park JH, McMillan DC, Powell AG, et al. Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer. Clin Cancer Res. 2015;21:882-8.
Fu M, Chen D, Luo F, et al. Association of the tumour stroma percentage in the preoperative biopsies with lymph node metastasis in colorectal cancer. Br J Cancer. 2020;122:388-96.
Hynes SO, Coleman HG, Kelly PJ, et al. Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study. Histopathology. 2017;71:12-26.
West NP, Dattani M, McShane P, et al. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer. 2010;102:1519-23.
Kobayashi H, Enomoto A, Woods SL, et al. Cancer-associated fibroblasts in gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2019;16:282-95.
Haasnoot KJC, Backes Y, Moons LMG, et al. Associations of non-pedunculated T1 colorectal adeno- carcinoma outcome with consensus molecular subtypes, immunoscore, and microsatellite status: a multicenter case-cohort study. Mod Pathol. 2020. https://doi.org/10.1038/s41379-020-0598-9.
PLOS Medicine Editors. Observational studies: getting clear about transparency. PLoS Med. 2014;11:e1001711.
Brierley J, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 8th ed. Chichester, UK: John Wiley; 2017.
Lugli A, Kirsch R, Ajioka Y, et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol. 2017;30:1299-311.
Kitajima K, Fujimori T, Fujii S, et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol. 2004;39:534-43.
Van Pelt GW, Kjaer-Frifeldt S, Van Krieken J, et al. Scoring the tumor-stroma ratio in colon cancer: procedure and recommendations. Virchows Arch. 2018;473:405-12.
Cohen JA. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20:37-46.
Onland-Moret NC, Van Der AD, Van Der Schouw YT, et al. Analysis of case-cohort data: a comparison of different methods. J Clin Epidemiol. 2007;60:350-5.
Rieder F, Brenmoehl J, Leeb S, et al. Wound healing and fibrosis in intestinal disease. Gut. 2007;56:130-9.
Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650-9.
Pai RK, Chen Y, Jakubowski MA, et al. Colorectal carcinomas with submucosal invasion (pT1): analysis of histopathological and molecular factors predicting lymph node metastasis. Mod Pathol. 2017;30:113-22.
Bourhis A, De Luca C, Cariou M, et al. Evaluation of KRAS, NRAS and BRAF mutational status and microsatellite instability in early colorectal carcinomas invading the submucosa (pT1): towards an in-house molecular prognostication for pathologists? J Clin Pathol. 2020;73:741-7.
Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582-98.
Tauriello DV, Calon A, Lonardo E, et al. Determinants of metastatic competency in colorectal cancer. Mol Oncol. 2017;11:97-119.
Berdiel-Acer M, Berenguer A, Sanz-Pamplona R, et al. A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer. Oncotarget. 2014;5:6437-52.
Calon A, Lonardo E, Berenguer-Llergo A, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015;47:320-9.
Isella C, Terrasi A, Bellomo SE, et al. Stromal contribution to the colorectal cancer transcriptome. Nat Genet. 2015;47:312-9.
Torres S, Bartolome RA, Mendes M, et al. Proteome profiling of cancer-associated fibroblasts identifies novel proinflammatory signatures and prognostic markers for colorectal cancer. Clin Cancer Res. 2013;19:6006-19.
Dunne PD, McArt DG, Bradley CA, et al. Challenging the cancer molecular stratification dogma: intratumoral heterogeneity undermines consensus molecular subtypes and potential diagnostic value in colorectal cancer. Clin Cancer Res. 2016;22:4095-104.
Kinchen J, Chen HH, Parikh K, et al. Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease. Cell. 2018;175:372-86.
Backes Y, Elias SG, Bhoelan BS, et al. The prognostic value of lymph node yield in the earliest stage of colorectal cancer: a multicenter cohort study. BMC Med. 2017;15:129.