Furukawa Taiji, Konishi Fumio, Shitoh Kazuhisa, Kojima Masayuki, Nagai Hideo, Tsukamoto Toshihiko
Department of Surgery, Jichi Medical School, Kawachi-gun, Tochigi, Japan.
Cancer. 2002 Feb 15;94(4):911-20.
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.
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 (MSI) was examined for 452 cases. TGF beta RII, immunohistochemical staining, and germline mutations of hMLH1 and hMSH2 were analyzed in high-frequency MSI cases.
High-frequency MSI 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 (33.3% 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 TGF beta RII 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).
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 TGF beta RII 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.
阿姆斯特丹标准在全球范围内用于遗传性非息肉病性结直肠癌（HNPCC）的临床诊断。在日本，已提出临床标准（JCC）以尽可能多地识别HNPCC病例，但JCC的适用性仍不确定。在本文中，作者回顾性评估JCC与贝塞斯达指南（BG）相比是否足以诊断HNPCC，并研究了HNPCC的有用筛查方法。
作者研究了452例结直肠癌病例，其中69例符合JCC（A组12例；B组57例），106例符合BG。对452例病例进行了微卫星不稳定性（MSI）检测。对高频MSI病例分析了TGFβRII、免疫组织化学染色以及hMLH1和hMSH2的种系突变。
21.7%（452例中的98例）发现高频MSI。在8例中检测到种系突变（hMLH1，3例；hMSH2，5例）。6例符合JCC（A组4例；B组2例），6例符合BG。JCCA组的种系突变率显著高于非JCCA组病例（33.3%对0.91%；P<0.001），发病年龄小于50岁的病例高于发病年龄大于50岁的病例（9.3%对0.27%，P<0.001）。所有种系突变携带者均有TGFβRII突变。免疫组织化学检测发现，hMLH1核染色减少的占57.3%（82例中的47例），hMSH2核染色减少的占18.3%（82例中的15例）。hMSH2减少的病例中预测种系突变的频率高于hMLH1减少的病例（33.3%对6.4%；P=0.016）。
JCCA适用于选择进行基因突变分析的病例，但JCCB在临床环境中无用。作者建议发病年龄小于50岁对筛查也很重要。对具有MSI表型的病例分析TGFβRII突变以及hMLH1或hMSH2的免疫组织化学染色，有助于选择应进行种系突变检测的病例。
