Methylation and microsatellite status and recurrence following adjuvant FOLFOX in colorectal cancer

被引:53
作者
Han, Sae-Won [1 ,2 ]
Lee, Hyun-Jung [1 ]
Bae, Jeong Mo [3 ]
Cho, Nam-Yun [3 ]
Lee, Kyung-Hun [1 ]
Kim, Tae-Yong [1 ]
Oh, Do-Youn [1 ,2 ]
Im, Seock-Ah [1 ,2 ]
Bang, Yung-Jue [1 ,2 ]
Jeong, Seung-Yong [4 ]
Park, Kyu Joo [4 ]
Park, Jae-Gahb [4 ]
Kang, Gyeong Hoon [3 ]
Kim, Tae-You [1 ,2 ,5 ]
机构
[1] Seoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
[2] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
[3] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea
[4] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea
[5] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea
关键词
methylation; microsatellite instability; colorectal cancer; oxaliplatin; III COLON-CANCER; DISEASE-FREE SURVIVAL; BRAF MUTATION; CHROMOSOMAL INSTABILITY; STAGE-II; PHENOTYPE; FLUOROURACIL; LEUCOVORIN; 5-FLUOROURACIL; THERAPY;
D O I
10.1002/ijc.27888
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The prognostic impact of CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP and MSI status in colorectal cancer patients treated with adjuvant FOLFOX. Stages II and III sporadic colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Eight CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, CDKN2A (p16), RUNX3 and SOCS1) and five microsatellite markers were examined. Disease-free survival (DFS) was analyzed according to CIMP and MSI status. A total of 322 patients were included: male/female 192/130, median age 61 years (range 3078), proximal/distal location 118/204 and Stages II/III 43/279. CIMP status was high in 25 patients (7.8%) and 21 patients (6.5%) had MSI-high tumor. CIMP/MSI status was not significantly associated with DFS: 3-year DFS 100% in CIMP()/MSI(+), 84% in CIMP()/MSI(), 82% in CIMP(+)/MSI() and 75% in CIMP(+)/MSI(+) (p = 0.33). Results of exploratory analysis showed that concurrent methylation at NEUROG1 and CDKN2A (p16) was associated with shorter DFS: 3-year DFS 69% in NEUROG1(+)/CDKN2A (p16)(+) versus 87% in NEUROG1()/CDKN2A (p16)() (p = 0.006). In conclusion, concurrent methylation of NEUROG1 and CDKN2A (p16) is associated with recurrence following adjuvant FOLFOX in Stages II/III colorectal cancer.
引用
收藏
页码:2209 / 2216
页数:8
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