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

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 [1-3]. 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 adenomacarcinoma 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.