????????????CpG??????

1
???????????-??2010
????????????CpG?????? ??????

• ??? ??
• ?????????? ????
• ???????????

1
2
????

• ????????????????????
• 30-40???????????????
• TNM????????????????????????
• ??SEER??????TNM????????????( ?A?????????????B?)?
• ?TNM?????,???????????????????????????????????,????
  ?????????????????????

2
3
????
?DNA??????? ??????????
????????
????
????????
???
?????????
???????
3
4
????
?????????????????
4
5
????
??????
?????CpG?????
?????
?????CpG????
???????????????p14 ?hMLH1?p16?MGMT?MINT1
5
6
????

• CpG??????(CIMP)???????????(CIN)???????(MSI)???????
  ??????????
• CIMP???????????????????
• CIMP()????????????????2/3?3/5?3/6?3/7????? ?
• ????CIMP???????????,????????
• ???????????????????(CIMP?CIN?MSI)?????????

6
7
????

• ???????????????????/???????????????
• ??????????????????

7
8
????

• 2004?7?-11???????????50??/???????????????
• ????
• ?????????
• ???????
• ????????
• ??????????

8
9
????-??????(IHC)

• ????k-ras?APC?p53?BAX?TGFßR?
• IHC???????
• ??????(k-ras?APC?Bax?TGFßR?)???(p53
  )?????????10???

??,???APC????,??????
9
10
????-???????(FCM)

• ?????????
• DNA??(DI)?????G0/1???? /?????G0/1????
• ???(DI1)????(DI?1)
• ???????CIN()

???
???
10
11
????- ??????(MSI)??

• ????BAT25?BAT26
• MSI?????
• ?????????(????)
• ????????????
• MSI() 2??????????????

MSI()
MSI(-)
11
12
????-??????PCR(MSP)

• ???? p14 ?hMLH1?p16?MGMT?MINT1
• MSP?????????
• ????PCR??????????????
• ??? PCR????????????,????????????
• CIMP() 3/5????????????

12
13
?????

• SPSS11.5??
• ????
• ???????????(DFS)
• ?????Kaplan-Meier?
• ?????Cox???
• ????P lt0.05

13
14
????-??????

• ????23?,??27??
• ????54.54 11.76?(22-80?)?
• ?????18?,???32??
• ???????5.24 2.53 cm(2-16cm)?
• ??????39?,????11??
• ????????36?,???14??
• ???????????()6?,????()4??
• TNM???A?11?, ?B?7?,??32??

14
15
????-????

• ????36??????5Fu???????3???
• ????????????3?,??????47.64 17.68??
• ??????13??5?????62?
• ????????3?,????19?,?????20?(??2??????????????)?5?
  ??????(DFS)58?

15
16
????-???????

• ??????
• CEA?????9?(gt10ug/l),CA19.9?????10?(gt37 U/ml)
• IHC??
• ???????k-ras(21?)?APC(20?)?p53(21?)?BAX(34?)?TGFß
  R?(29?)
• ????
• ???16?,???33?,1??CV???8???????
• MSI?? MSI()?6?(12)
• MSP??
• ?????????hMLH1(7?),MGMT(14?),p16(13?),p14(15?),MI
  NT1(27?)?
• CIMP()?12?(24)?

16
17
????-DFS????(??????)
?? p ? p ?
?? Kaplan-Meier Cox Regression
?? (60?, gt60?) 0.815 /
?? (?,?) 0.990 /
?? (??,??) 0.111 /
????? (3.0cm, gt3.0cm) 0.620 /
????(??,????) 0.671
????(????,???) 0.681 /
????(??,??) 0.128 /
????(??,??) 0.723 /
TNM??(??, ??) 0.049 0.175
????(?,?) 0.781 /
17
18
????- DFS????(???????)
?? P ? P ?
?? Kaplan-Meier Cox Regression
CEA(??,??) 0.304 /
CA19.9(??,??) 0.141 /
IHC-kras (??,??) 0.657 /
IHC-APC (??,??) 0.596 /
IHC-p53 (??,??) 0.700 /
IHC-BAX (??,??) 0.577 /
IHC-TGFßR? (??,??) 0.434 /
??(???,???) 0.997 /
MSI(??,??) 0.988 /
18
19
????- DFS????(???????)
?? P? P?
?? Kaplan-Meier Cox Regression
MSP-hMLH1(??,??) 0.691 /
MSP-MGMT(??,??) 0.885 /
MSP-p16(??,??) 0.027 /
MSP-p14(??,??) 0.422 /
MSP-MINT1(??,??) 0.356 /
CIMP 0.014 0.019 HR(95CI)2.935(1.193-7.220)
19
20
????- DFS????(CIMP)
5y-DFS 66
5y-DFS 30

• ?/????????????????(Kaplan-Meier?)

20
21
??-CIMP??????????

• ?????CIMP??????????????????
• ??????CIMP????????,?????????
• J Clin Oncol(2003) 2137293736
• Clin Cancer Res(2007) 1360936098
• Cancer Res(2008) 688541-8546
• ??????CIMP????????
• Gut (2009)589096
• ??????CIMP???????
• Virchows Arch (2009) 455485494
• ?????????????
• ?????panel???
• CIMP???????
• ??????MSP?MethyLight?Pyrosequencing ?

21
22
??-?????????????????

• ??????CIMP?5?panel???,p16?????????????????????????
  ????
• p16????????????,???????Cyclin D????CDK4/6,??Rb????
  ????,????????????
• p16?????CpG??????????????,?????CDK4/6?????,???????
  ??
• ????????p16?????????????,?????????
• Clin Cancer Res(2007)136093-6098
• J Cancer Res Clin Oncol(2010)136323-331

22
23
??- MSI??????????

• ??????MSI???????????????
• ???????MSI?????,???????,MSI?????(?6?)???
• CIMP????MSI??????????
• ???????????????40???
• ??????MSI???10-15?
• CIMP????20-40?

23
24
??-???????

• ??????????
• ?????????????????????????,???????CIMP??????panel
  ,?????CIMP?????????

24
25
??

• CIMP???????????????????????
• P16???????????????????????????

25
26
? ? !
26