Volume 9 Supplement 1

Proceedings of the 14th Annual Meeting of the Collaborative Group of the Americas on Inherited Colorectal Cancer

Open Access

Colorectal cancer in hyperplastic polyposis syndrome: In search of the polyp of origin

  • Christophe Rosty1, 2Email author,
  • Michael D Walsh2,
  • Neal I Walker3,
  • Mark A Jenkins4,
  • John L Hopper4,
  • Kevin Sweet5,
  • Susan Parry6,
  • Daniel D Buchanan2 and
  • Joanne P Young2
Hereditary Cancer in Clinical Practice20119(Suppl 1):O7

https://doi.org/10.1186/1897-4287-9-S1-O7

Published: 10 March 2011

Background

Hyperplastic polyposis syndrome (HPS) is a colorectal cancer (CRC) predisposition of unknown genetic aetiology that is characterised by the presence of multiple serrated polyps throughout the colon, and an increased risk of having a first-degree relative with CRC [13]. Though there is a trend for association between CRC and a higher number of polyps, patients with at least one colonic conventional adenoma have an increased risk of CRC compared to patients without conventional adenoma (odds ratio: 3.6) [2]. HPS was first thought to represent the familial model for the serrated neoplasia pathway, as an analogy to the familial adenomatous polyposis syndrome for the adenoma-carcinoma pathway. However, CRC in HPS patients appears to arise from both conventional adenomas and serrated polyp subtypes. To further define the carcinogenesis of HPS related colorectal neoplasia, we sought to characterise the histological features and the molecular alterations of the different types of benign polyps arising in HPS patients both in contiguity with and remote from CRC.

Methods

A total of 151 patients diagnosed with at least 5 serrated polyps outside the rectum were recruited from high-risk genetics clinics. Polyp counts were extracted from colonoscopy reports. Polyps, including contiguous polyps, and CRCs underwent pathology review and testing for KRAS codon 12 and 13 and BRAF V600E somatic mutations.

Results

CRC was identified in 56 patients (37%) with 31/56 (55%) being females. The mean polyp count in patients with CRC was 58, and their mean age was 52 years. A total of 65 CRCs were available for analysis. Where site was known, most CRCs 43/61 (71%) arose in the proximal colon; however, only 19/58 (33%) of CRCs demonstrated a BRAF V600E mutation. Somatic KRAS mutations were less frequent at 9/48 (19%). Contiguous polyp was seen in 16/53 (30%) evaluable CRCs, and of these 4 (25%) were tubular adenomas, 5 (31%) were tubulo-villous adenomas and 1 (6%) was a villous adenoma. Overall 10/16 (63%) showed conventional adenomatous morphology whereas 6/16 (37%) had serrated morphology. BRAF mutation was present in 5/16 (31%). CRC was present in more than one-third of clinic-based individuals who presented with multiple serrated polyps.

Conclusion

Despite a high serrated polyp count, only one-third of these CRCs demonstrated a BRAF V600E mutation, the molecular hallmark of the serrated neoplasia pathway, suggesting that though multiple serrated polyps act as a marker of an abnormal mucosa, the majority of CRC in these patients may arise through other mechanisms.

Authors’ Affiliations

(1)
Department of Molecular and Cellular Pathology, University of Queensland Centre for Clinical Research
(2)
Familial Cancer Laboratory, Queensland Institute for Medical Research
(3)
Envoi Pathology
(4)
Centre for MEGA Epidemiology, School of Population Health, University of Melbourne
(5)
Division of Human Genetics, Ohio State University
(6)
Department of Gastroenterology, Middlemore Hospital

References

  1. Boparai KS, Reitsma JB, Lemmens V, van Os TA, Mathus-Vliegen EM, Koornstra JJ, Nagengast FM, van Hest LP, Keller JJ, Dekker E: Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome. Gut 2010. [Epub ahead of print]Google Scholar
  2. Buchanan DD, Sweet K, Musa D, Jenkins M, Win AK, English DR, Walsh M, Clendenning M, McKeone D, Walters R, et al.: Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: a cross-sectional case series from genetics clinics. Plos One, in press.Google Scholar
  3. Jass JR: Colorectal polyposes: from phenotype to diagnosis. Pathol Res Pract 2008, 204: 431–447. 10.1016/j.prp.2008.03.008PubMedView ArticleGoogle Scholar

Copyright

© Rosty et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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