HNPCC-associated small bowel cancer:: Clinical and molecular characteristics
HNPCC-associated small bowel cancer:: Clinical and molecular characteristics
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DOI：
10.1053/j.gastro.2004.12.051
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发表时间：
2005-03-01
期刊：
影响因子：
29.4
通讯作者：
Speer, R
中科院分区：
文献类型：
--
作者：
Schulmann, K;Brasch, FE;Speer, R
背景与目的：遗传性非息肉病性结直肠癌（HNPCC）患者发生小肠癌（SBC）的风险显著增加。HNPC相关的SBC的特征很差。方法：根据临床、病理和生殖系突变数据对32例SBC进行表征。对17例SBC的组织形态学特征、微卫星不稳定性（MSI）检测、错配修复（MMR）蛋白表达和7个编码单核苷酸重复序列的移码突变进行了研究。结果：诊断时的中位年龄为39岁。50%的SBCs位于十二指肠。50%的患者符合阿姆斯特丹标准; 45%的患者没有既往恶性肿瘤的个人病史。2例患者有SBC阳性家族史。81%的病例中发现了致病性生殖系突变，95%的病例中检测到高MSI，89%的病例中MMR蛋白表达缺失。TGFBR 2、BAX、MSH 3、MSH 6、ACVR 2、AIM 2和SEC 63移码突变的检出率分别为69%、59%、59%、35%、82%、56%和56%。75%的患者肿瘤边缘呈扩张性生长，肿瘤内淋巴细胞浸润明显。结论：HNPC相关的SBC常在年轻时出现，可能是首发疾病表现。内窥镜可以检测到50%的肿瘤。考虑到最近的胃癌数据，我们建议从30岁开始对突变携带者进行内镜筛查，因为临床标准不能定义高危组。此外，我们的研究表明，HNPCC的组织病理学标准，MSI和MMR免疫组化往往与这些特征相似。
Background & Aims: The risk for small bowel cancer (SBC) is significantly increased in hereditary non polyposis colorectal cancer (HNPCC). HNPCC-associated SBCs are poorly characterized. Methods: Thirty-two SBCs were characterized according to clinical, pathologic, and germline mutation data. Histomorphologic characteristics, microsatellite instability (MSI) testing, mismatch repair (MMR) protein expression, and frameshift mutations of 7 coding mononucleotide repeats were investigated in 17 SBCs. Results; Median age at diagnosis was 39 years. Fifty percent of SBCs were located in the duodenum. The Amsterdam criteria were fulfilled in 50% of patients; 45% of patients had no personal history of previous malignancies. Two patients had a positive family history for SBC. Pathogenic germline mutations were identified in 81%; high MSI was detected in 95% and loss of MMR protein expression in 89% of cases. TGFBR2, BAX, MSH3, MSH6, ACVR2, AIM2, and SEC63 frameshift mutations were detected in 69%, 59%, 59%, 35%, 82%, 56%, and 56%, respectively. An expansive growth pattern of the tumor border and an intense intratumoral lymphocytic infiltrate were present in 75%, respectively. Conclusions: HNPCC-associated SBC often manifests at a young age and may be the first disease manifestation. Endoscopy may detect 50% of tumors. Considering recent data on gastric cancer, we propose endoscopic screening of mutation carriers starting at 30 years of age because clinical criteria cannot define a high-risk group. In addition, our study shows that histopathologic criteria, MSI, and MMR immunohistochemistry are often similar to these features in HNPCC.