Luo Ding-cun, Cai Qi, Sun Meng-hong, Ni Yao-zhong, Tao Chong-wei, Chen Zhe-jing, Shi Da-ren
Department of Surgical Oncology, Second Peoples' Hospital of Wenzhou, Wenzhou 325028, China.
Zhonghua Wai Ke Za Zhi. 2004 Feb 7;42(3):158-62.
To study the clinicopathological and molecular genetic characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), to enable the early diagnosis and to evaluate the treatment.
We analyzed 12 families of HNPCC from Wenzhou, Zhejiang province, China. Mismatch repair genes hMSH2 and hMLH1 expression and microsatellite instability of tumor tissue were studied using microdissection, microsatellite analysis, immunohistochemical staining and Gene Scan analysis. Direct DNA sequencing of hMSH2 and hMLH1 were performed subsequently.
Altogether 32 patients with colorectal cancer were recognized in 12 HNPCC families, with the median age of 45.2 years (75.0% before the age of 50 years). The proximal tumors accounted for 51.1%, while multiple colorectal cancers accounted for 34.4%. Poor differentiation cancers occupied half of the patients (53.1%). And 68.8% of the patients had the tumor of Dukes A and B. Among 12 HNPCC families, 7 cases in 6 HNPCC families developed extracolonic cancer. 13 cases died during follow up of 1 - 23 years. The median survival time was 6.4 years. 19 alive cases followed up from 1 to 28 years. All tumors (9/9) displayed microsatellite instability, with the half losing hMSH2 or hMLH1 expression. In the 5 genetic analyzed kindreds 3 possessed germline mutation. Two of three mutations have not been reported in the worldwide database previously.
HNPCC showed distinct clinicopathological characteristics. Microsatellite instability analysis and immunohistochemical staining might be the effective screening methods before direct DNA sequencing for the detection of mutation in mismatch repair genes. It is important to analyze the members of affected families.
研究遗传性非息肉病性结直肠癌（HNPCC）的临床病理及分子遗传学特征，以实现早期诊断并评估治疗效果。
我们分析了来自中国浙江省温州市的12个HNPCC家系。采用显微切割、微卫星分析、免疫组织化学染色和基因扫描分析等方法，研究肿瘤组织中错配修复基因hMSH2和hMLH1的表达及微卫星不稳定性。随后对hMSH2和hMLH1进行直接DNA测序。
12个HNPCC家系中共识别出32例结直肠癌患者，中位年龄为45.2岁（75.0%在50岁之前）。近端肿瘤占51.1%，同时多原发性结直肠癌占34.4%。低分化癌占患者总数的一半（53.1%）。68.8%的患者肿瘤为Dukes A和B期。在12个HNPCC家系中，6个家系的7例患者发生了结外癌。13例患者在1至23年的随访期间死亡。中位生存时间为6.4年。19例存活患者的随访时间为1至28年。所有肿瘤（9/9）均显示微卫星不稳定性，其中一半失去hMSH2或hMLH1表达。在5个进行基因分析的家系中，3个家系存在种系突变。3个突变中有2个此前在全球数据库中未被报道。
HNPCC具有独特的临床病理特征。微卫星不稳定性分析和免疫组织化学染色可能是在直接DNA测序之前检测错配修复基因突变的有效筛查方法。对受累家系成员进行分析很重要。
