• I Ubink, W J van Eden, P Snaebjornsson, Kok N F M NFM Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., J van Kuik, W M U van Grevenstein, M M Laclé, J Sanders, Fijneman R J A RJA Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., S G Elias, Borel Rinkes I H M IHM Department of Surgical Oncology, Cancer Centre, University Medical Centre Utrecht, Utrecht, The Netherlands., Aalbers A G J AGJ Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., and O Kranenburg.
• Department of Surgical Oncology, Cancer Centre, University Medical Centre Utrecht, Utrecht, The Netherlands.
• Br J Surg. 2018 Jan 1; 105 (2): e204-e211.

BackgroundPatients 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.MethodsFresh-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.ResultsColorectal 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.ConclusionSignificant 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.© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

44 keywords...

hide…