TY - JOUR
T1 - Histopathological and molecular classification of colorectal cancer and corresponding peritoneal metastases
AU - Ubink, I.
AU - van Eden, W. J.
AU - Snaebjornsson, P.
AU - Kok, N. F.M.
AU - van Kuik, J.
AU - van Grevenstein, W. M.U.
AU - Laclé, M. M.
AU - Sanders, J.
AU - Fijneman, R. J.A.
AU - Elias, S. G.
AU - Borel Rinkes, I. H.M.
AU - Aalbers, A. G.J.
AU - Kranenburg, O.
N1 - Funding Information:
The authors acknowledge the NKI-AVL Core Facility Molecular Pathology and Biobanking for supplying NKI-AVL Biobank material. I.U. is supported by a grant from the Dutch Cancer Society (UU2014-6617). Disclosure: The authors declare no conflict of interest.
Publisher Copyright:
© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Patients with colorectal peritoneal carcinomatosis have a very poor prognosis. The recently developed consensus molecular subtype (CMS) classification of primary colorectal cancer categorizes tumours into four robust subtypes, which could guide subtype-targeted therapy. CMS4, also known as the mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4 status and histopathological features of colorectal peritoneal carcinomatosis were investigated in this study. Methods: Fresh-frozen tissue samples from primary colorectal cancer and paired peritoneal metastases from patients who underwent cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy were collected. Histopathological features were analysed, and a reverse transcriptase–quantitative PCR test was used to assess CMS4 status of all collected lesions. Results: Colorectal peritoneal carcinomatosis was associated with adverse histopathological characteristics, including a high percentage of stroma in both primary tumours and metastases, and poor differentiation grade and high-grade tumour budding in primary tumours. Furthermore, CMS4 was significantly enriched in primary tumours with peritoneal metastases, compared with unselected stage I–IV tumours (60 per cent (12 of 20) versus 23 per cent; P = 0.002). The majority of peritoneal metastases (75 per cent, 21 of 28) were also classified as CMS4. Considerable intrapatient subtype heterogeneity was observed. Notably, 15 of 16 patients with paired tumours had at least one CMS4-positive tumour location. Conclusion: Significant enrichment for CMS4 was observed in colorectal peritoneal carcinomatosis. Surgical relevance Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival of selected patients with colorectal peritoneal carcinomatosis, but recurrence is common. Histopathological and molecular analysis of colorectal peritoneal carcinomatosis could provide clues for development of novel therapies. In this study, colorectal peritoneal carcinomatosis was found to be enriched for tumours with high stromal content and CMS4-positive status. To further improve prognosis for patients with colorectal peritoneal carcinomatosis, therapies that target tumour–stroma interaction could be added to CRS-HIPEC.
AB - Background: Patients with colorectal peritoneal carcinomatosis have a very poor prognosis. The recently developed consensus molecular subtype (CMS) classification of primary colorectal cancer categorizes tumours into four robust subtypes, which could guide subtype-targeted therapy. CMS4, also known as the mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4 status and histopathological features of colorectal peritoneal carcinomatosis were investigated in this study. Methods: Fresh-frozen tissue samples from primary colorectal cancer and paired peritoneal metastases from patients who underwent cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy were collected. Histopathological features were analysed, and a reverse transcriptase–quantitative PCR test was used to assess CMS4 status of all collected lesions. Results: Colorectal peritoneal carcinomatosis was associated with adverse histopathological characteristics, including a high percentage of stroma in both primary tumours and metastases, and poor differentiation grade and high-grade tumour budding in primary tumours. Furthermore, CMS4 was significantly enriched in primary tumours with peritoneal metastases, compared with unselected stage I–IV tumours (60 per cent (12 of 20) versus 23 per cent; P = 0.002). The majority of peritoneal metastases (75 per cent, 21 of 28) were also classified as CMS4. Considerable intrapatient subtype heterogeneity was observed. Notably, 15 of 16 patients with paired tumours had at least one CMS4-positive tumour location. Conclusion: Significant enrichment for CMS4 was observed in colorectal peritoneal carcinomatosis. Surgical relevance Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival of selected patients with colorectal peritoneal carcinomatosis, but recurrence is common. Histopathological and molecular analysis of colorectal peritoneal carcinomatosis could provide clues for development of novel therapies. In this study, colorectal peritoneal carcinomatosis was found to be enriched for tumours with high stromal content and CMS4-positive status. To further improve prognosis for patients with colorectal peritoneal carcinomatosis, therapies that target tumour–stroma interaction could be added to CRS-HIPEC.
UR - http://www.scopus.com/inward/record.url?scp=85040735570&partnerID=8YFLogxK
U2 - 10.1002/bjs.10788
DO - 10.1002/bjs.10788
M3 - Article
AN - SCOPUS:85040735570
SN - 0007-1323
VL - 105
SP - e204-e211
JO - British Journal of Surgery
JF - British Journal of Surgery
IS - 2
ER -