Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma
Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma
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DOI：
10.1002/cncr.10332
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发表时间：
2002-02-15
期刊：
影响因子：
6.2
通讯作者：
Tsukamoto, T
中科院分区：
文献类型：
--
作者：
Furukawa, T;Konishi, F;Tsukamoto, T
背景：遗传性非息肉病性结直肠癌（HNPCC）的临床诊断在世界范围内普遍采用阿姆斯特丹标准。在日本，临床标准（JCC）已被提出，以确定尽可能多的HNPCC病例，但JCC的适用性仍然不确定。本文回顾性评价JCC与Bethesda指南（BG）相比是否足以诊断HNPCC，并探讨HNPCC的有用筛查方法。本文分析了452例大肠癌，其中符合JCC标准的69例（A组12例，B组57例），符合BG标准的106例。对452例患者进行了微卫星不稳定性（NISI）检测。在高频率MSI病例中分析了TGF β RII、免疫组化染色和hMLH 1和hMSH 2的种系突变。在21.7%（98/452）中发现了高频TMSI。在8例病例中检测到生殖系突变（hMLH 1，3例，hMSH 2; 5例）。6例病例符合JCC（A，4例; B，2例），6例符合BG。JCCA组的生殖系突变率显著高于非JCCA组（33.37。与0.91%相比，P < 0.001），发病年龄小于50岁的病例比大于50岁的病例（9.3%与0.27%，P < 0.001）。所有生殖系突变携带者都有TGF β RII突变。免疫组化显示，hMLH 1和hMSH 2的细胞核染色分别为57.3%（47/82）和18.3%（15/82）。在hMSH 2降低的病例中，预测的生殖细胞突变频率高于hMLH 1（33.3% vs. 6.4%; P = 0.016）。JCCA适用于选择病例进行基因突变分析，但JCCB不适用于临床环境。作者认为，发病年龄小于50岁对筛查也很重要。分析TGFbetaRII突变和hMLH 1或hMSH 2的免疫组化染色的MSI表型的情况下，是有用的，选择的情况下，应该测试生殖系突变。(C)2002年美国癌症协会。
BACKGROUND, The Amsterdam criteria are used worldwide for the clinical diagnosis of hereditary nonpolyposis colorectal carcinoma (HNPCC). In Japan, clinical criteria (JCC) have been proposed to identify as many HNPCC cases as possible, but the suitability of the JCC remains uncertain. In this article, the authors evaluate retrospectively whether the JCC are adequate to diagnose HNPCC compared with the Bethesda guidelines (BG) and also investigated useful screening methods for HNPCC.METHODS. The authors studied 452 colorectal carcinoma cases, of which 69 cases fulfilled the JCC (A, 12; B, 57) and 106 fulfilled the BG. Microsatellite instability (NISI) was examined for 452 cases. TGFbetaRII, immunohistochemical staining, and germline mutations of hMLH1 and hMSH2 were analyzed in high-frequency MSI cases.RESULTS. High-frequency TMSI was found in 21.7% (98 of 452). Germline mutations were detected in eight cases (hMLH1, three, hMSH2; five). Six cases fulfilled the JCC (A, four; B, two), and six fulfilled the BG. The germline mutation rate was significantly higher in the JCCA than in non-JCCA cases (33.37. vs. 0.91%; P < 0.001) and in cases with an age at onset younger than 50 years than older than 50 years (9.3% vs. 0.27%, P < 0.001). All germline mutation carriers had the TGFbetaRII mutation. Immunohistochemically, a decreased nuclear staining was found in 57.3% (47 of 82) for hMLH1 and in 18.3% (15 of 82) for hMSH2. The frequency of predicted germline mutations was higher in cases with decreased hMSH2 than hMLH1 (33.3% vs. 6.4%; P = 0.016).CONCLUSIONS. The JCCA are suitable for selecting cases to analyze for gene mutations, but the JCCB are not useful for the clinical setting. The authors suggest that an age at onset younger than 50 years is also important for screening. Analyzing TGFbetaRII mutations and immunohistochemical staining of hMLH1 or hMSH2 for cases with MSI phenotype are useful for selecting cases who should be tested for germline mutations. (C) 2002 American Cancer Society.