Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients.
Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients.
复制标题
DOI：
10.1002/cncr.24913
复制
发表时间：
2010-04-01
期刊：
影响因子：
6.2
通讯作者：
O'Connell, Michael J.
中科院分区：
文献类型：
--
作者：
Sinicrope, Frank;Foster, Nathan R.;Sargent, Daniel J.;Thibodeau, Stephen N.;Smyrk, Thomas C.;O'Connell, Michael J.
关键词：
Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil-based adjuvant chemotherapy. We developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. TNM stage II and III colon carcinomas (n= 982) from six 5-fluorouracil-based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor infiltrating lymphocytes (TILs) were quantitated (n= 326). Logistic regression and a recursive partitioning and amalgamation (RPA) analysis were used to identify predictive factors for MMR status. Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13/468); proximal tumors had a greater likelihood (26%; 130/506). Using tumor site, grade, and gender, the logistic regression model showed excellent discrimination (c-statistic = 0·81). Proximal site, female gender, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n= 326), a model including proximal site, TILs (> 2 / HPF), and female gender showed even better discrimination (c-statistic =0·86) with a PPV of 81%. Defective MMR is rare in distal, sporadic colon cancers that should generally not undergo MMR testing. Proximal site, poor differentiation, and female gender detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decision-making.
登录
查看更多内容
影响因子：
3.4
作者：
O'Connell, Michael J.;Sargent, Daniel J.;Kugler, John W.
通讯作者：
Kugler, John W.
影响因子：
24.5
作者：
Jass, JR;Do, KA;Leggett, B
通讯作者：
Leggett, B
影响因子：
45.3
作者：
Lanza, Giovanni;Gafa, Roberta;Cavazzini, Luigi
通讯作者：
Cavazzini, Luigi
影响因子：
29.4
作者：
Jenkins, Mark A.;Hayashi, Shinichi;Jass, Jeremy R.
通讯作者：
Jass, Jeremy R.
影响因子：
45.3
作者：
Lynch, Henry T.;Boland, C. Richard;Lynch, Patrick M.
通讯作者：
Lynch, Patrick M.