Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma.

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.

Furukawa T ，Konishi F ，Shitoh K ，Kojima M ，Nagai H ，Tsukamoto T ... -  《CANCER》

Identification of concurrent germ-line mutations in hMSH2 and/or hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds.

Nakahara M ，Yokozaki H ，Yasui W ，Dohi K ，Tahara E ... -  《CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION》

Two types of sporadic multiple colorectal cancers with and without HNPCC-like genetic instability.

Komura K ，Masuda H ，Esumi M 《hepato-gastroenterology》

[Mutation analysis of hMSH2 and hMLH1 genes in Chinese hereditary nonpolyposis colorectal cancer families].

Cai Q ，Sun MH ，Fu G ，Ding CW ，Mo SJ ，Cai SJ ，Ren SX ，Min DL ，Xu XL ，Zhu WP ，Zhang TM ，Shi DR ... -  《-》

[Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients].

Liu SR ，Wang ZJ ，Zhao B ，Wan YL ，Huang YT ... -  《-》