Comparison of the clinical prediction model PREMM(1,2,6) and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer.
Comparison of the clinical prediction model PREMM(1,2,6) and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer.
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DOI：
10.1136/gutjnl-2011-301265
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发表时间：
2013-02
期刊：
影响因子：
24.5
通讯作者：
Colon Cancer Family Registry
中科院分区：
文献类型：
--
作者：
Kastrinos F;Steyerberg EW;Balmaña J;Mercado R;Gallinger S;Haile R;Casey G;Hopper JL;LeMarchand L;Lindor NM;Newcomb PA;Thibodeau SN;Syngal S;Colon Cancer Family Registry
Lynch综合征是由生殖细胞错配修复（MMR）基因突变引起的。PREMM 1，2，6模型根据个人和家族癌症史预测MMR基因突变的可能性。比较使用PREMM 1、2、6和肿瘤检测（微卫星不稳定性（MSI）和/或免疫组织化学（IHC）染色）识别突变携带者的策略。分析了通过结肠癌家族登记处登记的基于人群或基于临床的结直肠癌患者的数据。评价包括MLH 1、MSH 2、MSH 6和PMS 2的MSI、IHC和种系突变分析。个人和家族癌症史被用来计算PREMM 1，2，6预测。使用受试者工作特征曲线（AUC）下的面积评估识别携带者与非携带者的区分能力。预测基于逻辑回归模型，用于（1）使用PREMM 1，2，6进行癌症评估，（2）MSI，（3）针对任何MMR蛋白表达丧失的IHC，（4）MSI + IHC，（5）PREMM 1，2，6 + MSI，（6）PREMM 1，2，6 + IHC，（7）PREMM 1，2，6 + IHC + MSI。在1651例受试者中，239例（14%）有突变（90例MLH 1，125例MSH 2，24例MSH 6）。PREMM 1、2、6区分良好，AUC 0.90（95% CI 0.88 - 0.92）。单独的MSI、单独的IHC或MSI + IHC各自具有较低的AUC：分别为0.77、0.82和0.82。IHC + PREMM 1、2、6的增加值略大于PREMM 1、2、6 + MSI（AUC 0.94 vs 0.93）。在PREMM 1、2、6 + IHC中添加MSI并不能提高辨别力。PREMM 1、2、6和IHC在区分突变携带者和非携带者方面表现出优异的性能，并且当组合时表现最好。MSI可能在区分Lynch综合征与其他家族性结直肠癌亚型中具有更大的作用，其中具有高PREMM 1，2，6评分，遗传评估未揭示MMR突变。
Lynch syndrome is caused by germline mismatch repair (MMR) gene mutations. The PREMM1,2,6 model predicts the likelihood of a MMR gene mutation based on personal and family cancer history. To compare strategies using PREMM1,2,6 and tumour testing (microsatellite instability (MSI) and/or immunohistochemistry (IHC) staining) to identify mutation carriers. Data from population-based or clinic-based patients with colorectal cancers enrolled through the Colon Cancer Family Registry were analysed. Evaluation included MSI, IHC and germline mutation analysis for MLH1, MSH2, MSH6 and PMS2. Personal and family cancer histories were used to calculate PREMM1,2,6 predictions. Discriminative ability to identify carriers from non-carriers using the area under the receiver operating characteristic curve (AUC) was assessed. Predictions were based on logistic regression models for (1) cancer assessment using PREMM1,2,6, (2) MSI, (3) IHC for loss of any MMR protein expression, (4) MSI + IHC, (5) PREMM1,2,6 + MSI, (6) PREMM1,2,6 + IHC, (7) PREMM1,2,6 + IHC + MSI. Among 1651 subjects, 239 (14%) had mutations (90 MLH1, 125 MSH2, 24 MSH6). PREMM1,2,6 discriminated well with AUC 0.90 (95% CI 0.88 to 0.92). MSI alone, IHC alone, or MSI + IHC each had lower AUCs: 0.77, 0.82 and 0.82, respectively. The added value of IHC + PREMM1,2,6 was slightly greater than PREMM1,2,6 + MSI (AUC 0.94 vs 0.93). Adding MSI to PREMM1,2,6 + IHC did not improve discrimination. PREMM1,2,6 and IHC showed excellent performance in distinguishing mutation carriers from non-carriers and performed best when combined. MSI may have a greater role in distinguishing Lynch syndrome from other familial colorectal cancer subtypes among cases with high PREMM1,2,6 scores where genetic evaluation does not disclose a MMR mutation.
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影响因子：
6.2
作者：
Reyes, CM;Allen, BA;Wilson, LS
通讯作者：
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影响因子：
9.8
作者：
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作者：
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作者：
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Phillips KA
影响因子：
29.4
作者：
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通讯作者：
Syngal S