Zivković Vesna, Katić Vuka, Gligorijević Jasmina, Andelković Zlatibor, Petrović Aleksandar, Krstić Miljan
Institut za patologiju, Medicinski fakultet Nis.
Med Pregl. 2008 Jan-Feb;61(1-2):79-82. doi: 10.2298/mpns0802079z.
Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndromes I and II, accounts for about 5-8% of colorectal cancers. Lynch syndrome I is an autosomal dominant inherited disorder characterized by early onset of colorectal cancer, predominance of proximal and multiple tumors, and microsatellite instability. In order to identify HNPCC, the international "Amsterdam criteria" have been used.
The proband was a 40-year-old male who was admitted to hospital with a diagnosis of advanced rectal cancer. Left colectomy was carried out. A histopathologic diagnosis of poorly differentiated adenocarcinoma of clinical stage Dukes C was made. The family talking was done and it was revealed that the proband had five family members (one of first degree relative) with colorectal cancer, and two successive generations affected. All malignancy were diagnosed before 45 years of age. In one family member, metachronous transverse cancer was revealed 12 years after surgery for cecal adenocarcinoma.
The main molecular cause for HNPCC is constitutional mutation in one of the mismatch repair (MMR) genes that regulate the excision of errors occurring during DNA replication. The most often are mutations of MLH1 and MSH2 genes, and microsatellite instability is present in about 90-95% HNPCC. In this report, we present a case of an HNPCC patient who met the Amsterdam criteria for Lynch syndrome I. Family members that fulfil the Amsterdam criteria should be investigated for mutation in MMR genes. The genetic tests are not routinely available, so colonoscopic screening of all asymptomatic family members older than 25 has been recommended.
遗传性非息肉病性结直肠癌（HNPCC），也称为林奇综合征I型和II型，约占结直肠癌的5 - 8%。林奇综合征I型是一种常染色体显性遗传疾病，其特征为结直肠癌发病早、近端和多发肿瘤占优势以及微卫星不稳定性。为了识别HNPCC，已采用国际“阿姆斯特丹标准”。
先证者为一名40岁男性，因晚期直肠癌入院。实施了左半结肠切除术。组织病理学诊断为临床分期为杜克C期的低分化腺癌。进行了家族访谈，结果显示先证者有5名家族成员（1名一级亲属）患有结直肠癌，且累及两代人。所有恶性肿瘤均在45岁之前确诊。在一名家族成员中，盲肠腺癌手术后12年发现异时性横结肠癌。
HNPCC的主要分子病因是调控DNA复制过程中发生错误切除的错配修复（MMR）基因之一的遗传性突变。最常见的是MLH1和MSH2基因的突变，约90 - 95%的HNPCC存在微卫星不稳定性。在本报告中，我们展示了一例符合林奇综合征I型阿姆斯特丹标准的HNPCC患者病例。符合阿姆斯特丹标准的家族成员应进行MMR基因突变检测。基因检测并非常规可用，因此建议对所有25岁以上无症状家族成员进行结肠镜筛查。
