Focus on: Gli altri tumori coinvolti nella Sindrome di Lynch
Cristina Oliani
ULSS5 OvestVicentino
Koornstra et al , Lancet Oncol 2009
HNPCC (Lynch Syndrome) rischio di cancro extra-colonico
Koornstra , Lancet Oncol 2009
•
> 10 %
Sede
Lifetime
risk%
Endometrio
27-71
Ovaio
3-14
Vie urinarie
1-28
Stomaco
2-30
Pancreas / v. biliari 2-18
•
< 10 %
Sede
Encefalo
Cute
Piccolo intestino
SIR
10-62
7-13
3-52
3-14
2-9
Lifetime
risk%
1-4
4
2-8
SIR
2-4
4
6
Median age
at diagnosis
46-62
40-47
49-60
47-56
43-66
Median age
at diagnosis
33-52
51
39-53
Koornstra et al , Lancet Oncol 2009
JCO Oct 1, 2009:
Engel C et al, 2012
Bonadona V et al, 2011
Watson P et al, 2008
Li-Hurtubise K.M. et al, 2013
Lynch
status
Germline
mutation
Number of patients diagnosed
No cancer
Total
Prostate
Bladder
Renal
Pelvis
Ureter
Kidney
MSH2
4
2
2
2
0
120
130
MLH1
0
1
2
2
0
136
141
MSH6
0
0
0
0
0
21
21
MSH2
3
4
3
2
2
261
275
MLH1
0
0
0
0
0
207
207
MSH6
1
0
0
0
0
46
47
Total
8
7
7
6
2
791
821
MSH2carrier age>50 years
4
2
2
2
0
62
72
MSH2 FDR age>50 years
3
4
3
2
2
115
129
Mutation carrier
Untested male
FDR
Barrow PJ et al, Fam Cancer 2013
Leongamornlert D et al, 2014
Grandval P. et al
Ko Win A. et al, JCO 2012
Walsh MD et al
Clin Cancer Res. 2010
Lotsari JE et al
Breast Cancer Res. 2012
THE PRECANCEROUS CASCADE
Tprmet
K-ras
p53
DCC
loss
C-erb-2
CIN Pathway
Normal
Epithelium
Wilson KT et al
Gastroenterology 2007
CTNNB1
CDKN2A
C-Myc
K-SAM
methylation
TGFBR2
erbB-2
C-MET
FHIT
TP-53
K-RAS
Gastritis/
Metaplasia
Adenoma
Metastatic
Cancer
Cancer
TGFBR2
MSI
Pathway
CDKN2A methylation
CDH1 methylatio
n
BAX, E2F4,
MSH6, IGFIIR
hMLH1 methylation
MMR inactivation
Correa P et al Cancer
Research, 1994
GASTRIC CANCER IN LYNCH SYNDROME
Capelle LG et al, Gastroenterology 2010
Int J Cancer 2006
JH.Haanstra et al, 2014
Kastrinos F. et al, 2009
Borelli I. et al, 2014
Everett JR et al, 2014
Shia J et al, 2013
Pande M et al et al, 2013
GUT, 2013
Burn J et al, The Lancet 2011
A.H.S. Gylling et al, 2008
Hennink S.D et al, 2013
Counselling in other
extra colonic cancers in HNPCC
• Discordant expert opinion and low compliance
• Tailor according to
‒ Distribution of cancers within the family
‒ Type of mutation
‒ Anticipation
(2)
(3)
(4)
(1) Stadler, ASCO 2009; Capelle, Gastroenterology 2010
(2) Koornstra, Lancet Oncol 2009
(3) Clyne, Br J Ca 2009; Wijnen, Gastroenterology 2009;
Ramsoekh, Her Ca Clin Pract, 2010; Shah, Cancer Res 2010
(4) Nilbert, JCO 2009; Gruber & Mukherjee, JCO 2009
(1)