IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas.
IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas.
复制标题
DOI：
10.1007/s00401-015-1398-z
复制
发表时间：
2015-04
影响因子：
12.7
通讯作者：
Aldape KD
中科院分区：
文献类型：
--
作者：
Olar A;Wani KM;Alfaro-Munoz KD;Heathcock LE;van Thuijl HF;Gilbert MR;Armstrong TS;Sulman EP;Cahill DP;Vera-Bolanos E;Yuan Y;Reijneveld JC;Ylstra B;Wesseling P;Aldape KD
弥漫性神经胶质瘤到目前为止是根据形态学分级的。最近的研究结果表明，异柠檬酸脱氢酶（IDH）突变状态定义生物学上不同的肿瘤组。肿瘤分级和有丝分裂指数在患者预后中的作用尚未在IDH突变状态分层后进行评估。为了解决这个问题，我们询问了558例WHO II-III级弥漫性胶质瘤的IDH 1/2突变，并独立研究了IDH突变和野生型肿瘤亚群中WHO分级的预后影响。与IDH-野生型肿瘤（HR=1.74，95% CI= 0.95-3.16）相比，IDH-突变型肿瘤中级别的预后影响是中等的[风险比（HR）=1.21，95%置信区间（CI）= 0.91-1.61]。使用4/1000肿瘤细胞的二分有丝分裂指数截止值，我们发现虽然有丝分裂指数与IDH-野生型肿瘤的结果显著相关，（对数秩p<0.0001，HR=4.41，95%CI =2.55-7.63），与IDH突变型肿瘤的结局无关（对数秩p=0.5157，HR=1.10，95%CI =0.80-1.51），并且可以证明IDH突变和有丝分裂指数之间的统计学相互作用（p<0.0001）（即，表明有丝分裂指数对患者结果的影响取决于IDH突变状态）。患者年龄是弥漫性胶质瘤的一个既定预后因素，仅在IDH野生型亚组中与预后显著相关，与先前数据一致，1 p/19 q共缺失可改善IDH突变队列的预后。这些发现表明，将II-III级胶质瘤分为由IDH突变的存在或不存在定义的亚组会导致具有不同预后特征的亚组。IDH突变型与IDH野生型弥漫性II-III级胶质瘤作为独立实体，有必要进一步评价分级标准和预后标志物。
Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II–III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and wild-type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR)=1.21, 95% confidence interval (CI)=0.91–1.61] compared to IDH-wild type tumors (HR=1.74, 95% CI=0.95–3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p<0.0001, HR=4.41, 95% CI=2.55–7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p=0.5157, HR=1.10, 95% CI=0.80–1.51), and could demonstrate a statistical interaction (p<0.0001) between IDH mutation and mitotic index (i.e. suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II–III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II–III gliomas as independent entities.
登录
查看更多内容
影响因子：
3.9
作者：
Ahmadi, Rezvan;Stockhammer, Florian;Hartmann, Christian
通讯作者：
Hartmann, Christian
影响因子：
4.8
作者：
Hendzel, MJ;Nishioka, WK;Th'ng, JPH
通讯作者：
Th'ng, JPH
影响因子：
11.5
作者：
Gorovets, Daniel;Kannan, Kasthuri;Huse, Jason T.
通讯作者：
Huse, Jason T.
影响因子：
64.8
作者：
Chin, L.;Meyerson, M.;Aldape, K.;Bigner, D.;Mikkelsen, T.;VandenBerg, S.;Kahn, A.;Penny, R.;Ferguson, M. L.;Gerhard, D. S.;Getz, G.;Brennan, C.;Taylor, B. S.;Winckler, W.;Park, P.;Ladanyi, M.;Hoadley, K. A.;Verhaak, R. G. W.;Hayes, D. N.;Spellman, Paul T.;Absher, D.;Weir, B. A.;Ding, L.;Wheeler, D.;Lawrence, M. S.;Cibulskis, K.;Mardis, E.;Zhang, Jinghui;Wilson, R. K.;Donehower, L.;Wheeler, D. A.;Purdom, E.;Wallis, J.;Laird, P. W.;Herman, J. G.;Schuebel, K. E.;Weisenberger, D. J.;Baylin, S. B.;Schultz, N.;Yao, Jun;Wiedemeyer, R.;Weinstein, J.;Sander, C.;Gibbs, R. A.;Gray, J.;Kucherlapati, R.;Lander, E. S.;Myers, R. M.;Perou, C. M.;McLendon, Roger;Friedman, Allan;Van Meir, Erwin G;Brat, Daniel J;Mastrogianakis, Gena Marie;Olson, Jeffrey J;Lehman, Norman;Yung, W. K. Alfred;Bogler, Oliver;Berger, Mitchel;Prados, Michael;Muzny, Donna;Morgan, Margaret;Scherer, Steve;Sabo, Aniko;Nazareth, Lynn;Lewis, Lora;Hall, Otis;Zhu, Yiming;Ren, Yanru;Alvi, Omar;Yao, Jiqiang;Hawes, Alicia;Jhangiani, Shalini;Fowler, Gerald;San Lucas, Anthony;Kovar, Christie;Cree, Andrew;Dinh, Huyen;Santibanez, Jireh;Joshi, Vandita;Gonzalez-Garay, Manuel L.;Miller, Christopher A.;Milosavljevic, Aleksandar;Sougnez, Carrie;Fennell, Tim;Mahan, Scott;Wilkinson, Jane;Ziaugra, Liuda;Onofrio, Robert;Bloom, Toby;Nicol, Rob;Ardlie, Kristin;Baldwin, Jennifer;Gabriel, Stacey;Fulton, Robert S.;McLellan, Michael D.;Larson, David E.;Shi, Xiaoqi;Abbott, Rachel;Fulton, Lucinda;Chen, Ken;Koboldt, Daniel C.;Wendl, Michael C.;Meyer, Rick;Tang, Yuzhu;Lin, Ling;Osborne, John R.;Dunford-Shore, Brian H.;Miner, Tracie L.;Delehaunty, Kim;Markovic, Chris;Swift, Gary;Courtney, William;Pohl, Craig;Abbott, Scott;Hawkins, Amy;Leong, Shin;Haipek, Carrie;Schmidt, Heather;Wiechert, Maddy;Vickery, Tammi;Scott, Sacha;Dooling, David J.;Chinwalla, Asif;Weinstock, George M.;O'Kelly, Michael;Robinson, Jim;Alexe, Gabriele;Beroukhim, Rameen;Carter, Scott;Chiang, Derek;Gould, Josh;Gupta, Supriya;Korn, Josh;Mermel, Craig;Mesirov, Jill;Monti, Stefano;Nguyen, Huy;Parkin, Melissa;Reich, Michael;Stransky, Nicolas;Garraway, Levi;Golub, Todd;Protopopov, Alexei;Perna, Ilana;Aronson, Sandy;Sathiamoorthy, Narayan;Ren, Georgia;Kim, Hyunsoo;Kong, Sek Won;Xiao, Yonghong;Kohane, Isaac S.;Seidman, Jon;Cope, Leslie;Pan, Fei;Van Den Berg, David;Van Neste, Leander;Yi, Joo Mi;Li, Jun Z.;Southwick, Audrey;Brady, Shannon;Aggarwal, Amita;Chung, Tisha;Sherlock, Gavin;Brooks, James D.;Jakkula, Lakshmi R.;Lapuk, Anna V.;Marr, Henry;Dorton, Shannon;Choi, Yoon Gi;Han, Ju;Ray, Amrita;Wang, Victoria;Durinck, Steffen;Robinson, Mark;Wang, Nicholas J.;Vranizan, Karen;Peng, Vivian;Van Name, Eric;Fontenay, Gerald V.;Ngai, John;Conboy, John G.;Parvin, Bahram;Feiler, Heidi S.;Speed, Terence P.;Socci, Nicholas D.;Olshen, Adam;Lash, Alex;Reva, Boris;Antipin, Yevgeniy;Stukalov, Alexey;Gross, Benjamin;Cerami, Ethan;Wang, Wei Qing;Qin, Li-Xuan;Seshan, Venkatraman E.;Villafania, Liliana;Cavatore, Magali;Borsu, Laetitia;Viale, Agnes;Gerald, William;Topal, Michael D.;Qi, Yuan;Balu, Sai;Shi, Yan;Wu, George;Bittner, Michael;Shelton, Troy;Lenkiewicz, Elizabeth;Morris, Scott;Beasley, Debbie;Sanders, Sheri;Sfeir, Robert;Chen, Jessica;Nassau, David;Feng, Larry;Hickey, Erin;Schaefer, Carl;Madhavan, Subha;Buetow, Ken;Barker, Anna;Vockley, Joseph;Compton, Carolyn;Vaught, Jim;Fielding, Peter;Collins, Francis;Good, Peter;Guyer, Mark;Ozenberger, Brad;Peterson, Jane;Thomson, Elizabeth
通讯作者：
Thomson, Elizabeth
影响因子：
2.2
作者：
Cairncross, Gregory;Jenkins, Robert
通讯作者：
Jenkins, Robert