M T A Strous1,2, T K E Faes3, A L H M Gubbels3, R L A van der Linden4, W E Mesker5, K Bosscha4, C M Bronkhorst6, M L G Janssen-Heijnen7,8, F J Vogelaar9, A P de Bruïne3. 1. Department of Surgery, VieCuri Medical Centre, Tegelseweg 210, 5912 BL, Venlo, The Netherlands. maudstrous@viecuri.nl. 2. Department of Epidemiology, GROW School for Oncology and Developmental Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. maudstrous@viecuri.nl. 3. Department of Pathology, VieCuri Medical Centre, Venlo, The Netherlands. 4. Department of Surgery, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. 5. Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands. 6. Department of Pathology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. 7. Department of Epidemiology, GROW School for Oncology and Developmental Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. 8. Department of Epidemiology, VieCuri Medical Center, Venlo, The Netherlands. 9. Department of Surgery, VieCuri Medical Centre, Tegelseweg 210, 5912 BL, Venlo, The Netherlands.
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.
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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