增生性息肉病的表型和分子特征。

Phenotypic and molecular characteristics of hyperplastic polyposis.

作者信息

Rashid A, Houlihan P S, Booker S, Petersen G M, Giardiello F M, Hamilton S R

机构信息

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

出版信息

Gastroenterology. 2000 Aug;119(2):323-32. doi: 10.1053/gast.2000.9361.

DOI:10.1053/gast.2000.9361

PMID:10930367

Abstract

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 admixed hyperplastic-adenomatous polyps from 13 patients with hyperplastic polyposis (more than 20 HPs), 5 patients with a large HP (>/=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 more 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 1p (4% vs. 17%, P = 0.03). K-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 1p 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 1p allelic loss in some HPs, in contrast to patients who have large, right-sided HPs or small numbers of HPs that lack 1p loss.

摘要

背景与目的

据报道，增生性息肉病患者有多个和/或大的增生性息肉（HP），患结直肠癌的风险增加，但增生性息肉病的表型和基因改变尚未得到详细研究。

方法

我们评估了13例增生性息肉病患者（超过20个HP）、5例有一个大HP（直径≥1 cm）的患者和5例有多个HP（5 - 10个HP）的患者的129个HP、6个锯齿状腺瘤和3个混合性增生性腺瘤性息肉的临床病理及分子特征。

结果

与左半结肠相比，右半结肠的HP中p21（Waf-1/Cip1）表达的地形失调更频繁（94%对76%，P = 0.03），增殖也更频繁（92%对53%，P = 0.0001），但1p染色体等位基因缺失频率较低（4%对17%，P = 0.03）。8%的HP存在K-ras突变，无p53基因产物过表达，3%有微卫星不稳定性，与同期癌中的微卫星不稳定性无关。有一个大HP的患者与有多个HP的患者不同，前者右侧HP频率高（63%对22%，P = 0.01），右侧结肠癌频率高（100%对8%，P = 0.003）。增生性息肉病与结直肠癌家族史相关（P = 0.01），且HP中1p染色体缺失相关（21%对0%，P = 0.001）。