Phenotypic and molecular characteristics of hyperplastic polyposis.
Phenotypic and molecular characteristics of hyperplastic polyposis.
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DOI：
10.1053/gast.2000.9361
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发表时间：
2000-08
期刊：
影响因子：
29.4
通讯作者：
Asif Rashid;P. S. Houlihan;S. Booker;G. M. Petersen;F. Giardiello;Stanley R. Hamilton
中科院分区：
文献类型：
--
作者：
Asif Rashid;P. S. Houlihan;S. Booker;G. M. Petersen;F. Giardiello;Stanley R. Hamilton
背景与目的增生性息肉病患者有多发和/或大型增生性息肉，结直肠癌的发病风险增加，但增生性息肉病的表型和遗传改变尚未得到详细研究。方法对13例增生性息肉(>20HPS)、5例较大Hp(直径<1 cm)、5例多发性HPS(5~10HPS)的129例HPS、6例锯齿状腺瘤和3例混合性增生性腺瘤性息肉的临床病理和分子生物学特征进行分析。结果右半结肠HPS中p21(WAF-1/Cip1)表达异常(94%比76%，P=0.03)，增殖异常(92%比53%，P=0)。0001)，但较少发生1p等位基因丢失(4%vs.17%，P=0.03)。K-ras基因突变在8%的HPS中存在，P53基因产物无一例过度表达，3%的HPS中微卫星不稳定性与微卫星不稳定性无关。幽门螺杆菌大的患者与多发幽门螺杆菌的患者相比，右侧幽门螺杆菌的发生率高(63%比22%，P=0.003)，右侧结肠癌的发生率高(100%比8%，P=0.003)。增生性息肉与结直肠癌家族史相关(P=0.001)，与Hp中1p染色体缺失相关(21%vs.0%，P=0.05)。结论增生性息肉/异型增生-腺癌序列可表现为3种不同的表型，包括增生性息肉和部分HPS的染色体1p等位基因缺失，而不是大的、右侧的HPS或缺乏1p丢失的少量HPS。
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.