Phenotypic and molecular characteristics of hyperplastic polyposis

Background & Aims: Patients with hyperplastic polyposis are reported to have multiple and/or large hyperplastic polyps (HPs) and an increased risk of colorectal cancer, but the phenotype and genetic alterations in hyperplastic polyposis have not been studied in detail. Methods: We evaluated clinical-pathological and molecular characteristics of 129 HPs, 6 serrated adenomas, and 3 admired hyperplastic-adenomatous polyps from 13 patients with hyperplastic polyposis (move than 20 HPs), 5 patients,with a large HP (greater than or equal to 1 cm in diameter), and 5 patients with multiple HPs (5-10 HPs). Results: HPs in the right colon in contrast to the left colorectum had move frequent topographic dysregulation of p21(Waf-1/Cip1) expression (94% vs. 76%, P = 0.03) and of proliferation (92% vs. 53%, P = 0.0001), but less frequent allelic loss of chromosome Ip (4% vs. 17%, P = 0.03). kappa-ras mutation was present in 8% of HPs, p53 gene product overexpression in none, and microsatellite instability in 3% without relationship to microsatellite instability in synchronous cancer, Patients with a large HP differed from those with multiple HPs in having a high frequency of right-sided HP (63% vs. 22%, P = 0.01) and of right-sided colon cancer (100% vs. 8%, P = 0.003). Hyperplastic polyposis was associated with a family history of colorectal cancer (P = 0.01) and with loss of chromosome Ip in HP (21% vs. 0%, P = 0.001). Conclusions: A hyperplastic polyp/dysplasia-to-adenocarcinoma sequence can be manifested in 3 distinct phenotypes consisting of patients with hyperplastic polyposis and chromosome Ip allelic loss in some HPs, in contrast to patients who have large, right-sided HPs or small numbers of HPs that lack Ip loss.