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Clin Epigenetics. 2017 Sep 5;9:97. doi: 10.1186/s13148-017-0397-4. eCollection 2017.

Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients.

Author information

1
Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway.
2
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
3
K.G Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.
4
Department of Chemistry, Biotechnology, and Food science, Norwegian University of Life Sciences, Ås, Norway.
5
Department of Hematology and Oncology, Stavanger University Hospital, PO Box 8100, 4068 Stavanger, Norway.
6
Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
7
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
8
Gastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, Stavanger, Norway.
#
Contributed equally

Abstract

BACKGROUND:

Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients.

RESULTS:

The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage (P = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P = 3.0E-4; time to recurrence P = 3.1E-4), although not significant. The same trend was observed in multivariate analyses (P = 1.4E-1 and P = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse.

CONCLUSIONS:

Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

KEYWORDS:

Biomarkers; DNA methylation; Occult metastases; Prognosis; Relapse; Sentinel lymph nodes

PMID:
28878843
PMCID:
PMC5584052
DOI:
10.1186/s13148-017-0397-4
[Indexed for MEDLINE]
Free PMC Article

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