Молекулярно-биологические маркеры в диагностике

-
- 2014»
2014
-
2010
•
Grade 1
G1 (“
2
”)
G2
•
Grade 3
G3
G3
Bosman FT, et al. WHO Classification of Tumours of the Digestive System. Lyon, France: IARC Press; 2010.
2
–
-
LDSV – Large Dense Core
Vesicles (100 nm)
SLMV – Synaptic-Like Micro
Vesicles (40–80 nm)
A
(MW 38000)
Golgi
SSTR
ER
Nucleus
Klöppel G. et al. International Collaboration on Neuroendocrine Tumours. Vienna, Austria. 2011.
3
–
-
LDSV – Large Dense Core
Vesicles (100 nm)
SLMV – Synaptic-Like Micro
Vesicles (40–80 nm)
A
(MW 38000)
Golgi
SSTR
ER
Nucleus
Klöppel G. et al. International Collaboration on Neuroendocrine Tumours. Vienna, Austria. 2011.
4
-
LDCV
G1/
G2 /
(synapto hisin)
G1/
G2 /
(NSE, PGP9.5)
G1/
G2 /
G1/
G2 /
G1/
G2 /
G1/
G2 /
G1/
G2 /
(chromogranin A
SLMV
A
)
Ki67
53
CD56
SSTR2
Rindi G., Bordy C.// Best Pract. Res. Clin. Gastroenterol.-2005.-19.-519-534.
5
–
-
•
•
•
•
•
•
•
«
»
•
6
–
-
•
•
•
•
•
•
•
«
»
•
7
(CgA)
(~90%)
CgA
Cg
CgA
(Syn)
CgA
Syn
Taupenot L, Harper KL, O’Connor DT. N Engl J Med. 2003;348:1134-1149.
8
-
•
(AE1/3)
•
)
AE1/3
• CD 56 (NCAM)
• Chromogranin A
• Synaptophysin
•
CgA
Syn
CgA
Syn
CD56
•
CgA
Syn
CD56
•
P
?
CD56
9
C
CgA
+
Syn
CD45+
CD20 +
PNET
D 99 +
S100 +
HMB 45+
10
-
G2
calcitonin,
bombesin, insulin,
glucagon,
somatostatin,
gastrin, pancreatic
polypeptide (PP),
vasoactive intestinal
peptide (VIP),
adrenocorticotrophic
hormone(ACTH),
serotonin,
:
ghrelin, cortistatin,
obestatin,
secretagogin
G2
,
D. S. Klimstra, I.R. Modlin, N.V. Adsay et al. Pathology Reporting of Neuroendocrine Tumors: Application of the Delphic Consensus Process to the
Development of a Minimum Pathology Data Set. // Am. J. Surg. Pathol. – 2010. -Vol.34, N 3, . 300-313.
11
TTF-1
Foregut
12Midgut
Isl-1
PDXPAX-6
Hindgut
CDX-2
DX-2;
F-1; ISL-1; PDX-1; PAX-6
Schmitt AM et al Am J Surg Pathol. 2008 Mar;32(3):420-5, La Rosa S et al Virchows Arch. 2004 Sep;445(3):248-54
12
–
-
•
•
•
•
•
•
•
«
»
•
13
Ki-67 (MIB-1)
2%
Grade
(ENETS/WHO/AJCC)
Grade
8%
(10 HPF)
Ki-67 (%)
G1
<2
G2
2-20
3-20
G3
>20
>20
70%
HPF- high power field = 2mm2, 40
Ki67 (MIB-1): %
2000
Virchows Archiv. 2006; 2007, Rindi G, et al.
JNCI 2012, Rindi et al.
14
n=146)
21,7
94,2
G1 (<3%)
66,7
G2 (3-20%)
G3 (>20%)
5,8
11,6
0
20
40
60
80
0
100
20
40
60
G2
80
G1-G3
KiKi-67
Grade 1
5%
G1
G2
G3
Grade 2
Ki-67
Grade 3
G3
50%
15
19 (CK19);
RP KIT (CD 117); p53; hASH-1
PR
C
n=57)
n=57)
100
90
80
70
60
50
40
30
20
10
0
100
90
80
70
60
50
40
30
20
10
0
-
-
PRPR+
PRPR-
-
PR+
50%
80%
%
Ki-67
CK19
Ki-
RP
0
0
0
16
PR
-
n=57)
-
C
PR
17
CRABP-I – Cellular Retinoic Acid Binding Protein-I
n=72)
•
CRABP1 (3-
•
CRABP1
•
CRABP1
Ki-67
G1
G2
Ki-67 – 12%
Ki-67 –
78,9% CRABP1
Ki-67
Ki-67 –75%
18
–
-
•
•
•
•
•
•
•
«
»
•
19
-
IGF1/2
TGF 1
TGFbR
complex
VEGF-R
AKT
CCN2
IGFR
complex
SMAC
LRP1
ERK
P38/cGMP
VEGF
mTOR
3
20
2%
Ki-67 (MIB-1)
Grade
%
-Somatostatin analogue
- -IFn -
G1
2
8%
<10
-STZ+5FU/Dox
-
G2
3-20
>10
70%
<55
- Cispl+Etoposide
G3
>20
-
>55
Virchows Archiv. 2006; 2007, Rindi G, et al.
JNCI 2012, Rindi et al.
21
SSTR1 – SSTR5
SSTR 1-5
•
SSTA
•
•
•
Delta (D)
•
•
SSTR
(SSTR1 – SSTR5)
SSTR 2A (UMB-1)
•
SSTR2A
•
SSTR
SSTA
22
(n=27)
SSTR2 23
mTOR; MGMT; p53/Rb; TS; IGF1-R; P16; Cyclin D1; VEGF/VEGFR2; Hedgehog pathway
p-mTOR
MGMT
–
I
-
-
– MGMT
/pAkt/mTOR
-
24
1154
Ka
23/2
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