Ferreira Sara, Claro Isabel, Lage Pedro, Filipe Bruno, Fonseca Ricardo, Sousa Rita, Francisco Inês, Chaves Paula, Albuquerque Cristina, Leitão Carlos Nobre
Department of Gastroenterology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, Entidade Pública Empresarial, Rua Professor Lima Basto, 1099-023, Lisbon, Portugal.
Dis Colon Rectum. 2008 Jun;51(6):909-15. doi: 10.1007/s10350-008-9224-5. Epub 2008 Feb 29.
Original Bethesda Guidelines proposed microsatellite instability analysis in colorectal adenomas from patients younger than aged 40 years to identify new cases of Lynch syndrome. We intended to evaluate the characteristics of colorectal adenomas from patients younger than aged 40 years to determine their microsatellite instability status and to correlate it with germline mutations in MLH1 and MSH2 genes.
Seventy-two adenomas from 58 patients were analyzed. Family history of colorectal cancer, location, and histology of adenomas were evaluated. Microsatellite instability testing was performed with BAT26 only or with the complete Bethesda panel. Germline mutational analysis was performed in MLH1 and MSH2 genes.
Thirty-five patients had a family history of colorectal cancer and 16 of them belonged to Amsterdam Criteria positive families. The remaining 23 presented with sporadic adenomas. Microsatellite instability was found in seven adenomas from seven different patients, all belonging to Amsterdam Criteria-positive families. In six of these patients, a pathogenic germline mutation was identified.
Adenomas diagnosed before aged 40 years presented microsatellite instability only in patients from families with clinical criteria for Lynch syndrome. According to our results, to detect new cases of Lynch syndrome, family history is more important than microsatellite instability testing in adenomas from young patients.
最初的贝塞斯达指南建议对40岁以下患者的大肠腺瘤进行微卫星不稳定性分析，以识别林奇综合征新病例。我们旨在评估40岁以下患者大肠腺瘤的特征，确定其微卫星不稳定性状态，并将其与MLH1和MSH2基因的种系突变相关联。
分析了58例患者的72个腺瘤。评估了结直肠癌家族史、腺瘤的位置和组织学。仅使用BAT26或完整的贝塞斯达检测板进行微卫星不稳定性检测。对MLH1和MSH2基因进行种系突变分析。
35例患者有结直肠癌家族史，其中16例属于阿姆斯特丹标准阳性家族。其余23例为散发性腺瘤。在来自7个不同患者的7个腺瘤中发现微卫星不稳定性，所有这些患者均属于阿姆斯特丹标准阳性家族。在其中6例患者中鉴定出致病性种系突变。
40岁之前诊断的腺瘤仅在具有林奇综合征临床标准家族的患者中出现微卫星不稳定性。根据我们的结果，对于检测林奇综合征新病例，家族史比年轻患者腺瘤中的微卫星不稳定性检测更重要。
