Shtabinskaya
T.T., Kendysh E.N.
Grodno
State Medical University, Belarus
The prognostic significance of the expression
of angiogenic markers in high-grade anenocarcinoma of the colon
The main criterion of the
degree of malignancy in pathologic diagnosis of adenocarcinoma of the colon
according to the "International histological classification of tumors of
the bowel" (WHO, Geneva, 2000) is the degree of differentiation of tumor
cells.
It should be noted that
patients with high-grade adenocarcinomas(HGA), even at similar scope
and nature of surgical intervention, the effectiveness of the treatment is
different: some patients live 5 years or more, while others - die early after
treatment on disease progression.
Purpose: to determine the
value of angiogenic markers expression in HGA of colon for the prognosis of the
disease.
Materials and methods: 16 cases of HGA were investigated.
The study was performed on
paraffin sections using antibodies to VEGF, CD 105, MMP-2, Erk2, iNOS, TGF-β, NRP1,
MMP-9 according to standard
procedure. Quantitation of the level of expression was described in the
previous article [1].
Statistical analysis was
performed using STATISTICA 10.0 (SNAXAR207F394425FA-Q).
Results: Due to the fact that the median adjusted disease-free survival (ADFS)
in patients with high grades of 1,5 (1,0-2,3) years, the relative risk of an
adverse outcome of disease calculation was performed for the 2-year time
period.
Indicators of relative risk for CD105, VEGFA, NRP1,
MMP-2, MMP-9, TGF-β, Erk2, iNOS in HGA depending on ADFS two years are
shown in Table 1.
Table 1 - Performance OR 105 for CD, VEGFA, NRP1, MMP-2, MMP-9, TGF-β, Erk2, iNOS in HGA depending on ADFS
|
Indicator |
ADFS |
RR (95%CI)) |
||||
|
Antigen |
Точка разделения |
<2 (n=8) |
≥2 (n=8) |
р |
||
|
CD105 |
vascular
endothelium |
≤0,610 |
1 (12,5%) |
3 (37,5%) |
0,443 |
0,4 (0,07-2,50) |
|
>0,610 |
7 (87,5%) |
5 (62,5%) |
0,339 |
2,3 (0,40-13,61) |
||
|
VEGFА |
overall |
≤0,894 |
5 (62,5%) |
4 (50%) |
0,201 |
1,3 (0,46-3,65) |
|
>0,894 |
3 (37,5%) |
4 (50%) |
0,703 |
0,7 (0,27-2,17) |
||
|
parenchymal |
≤0,673 |
1 (12,5%) |
4 (50%) |
0,833 |
0,3 (0,05-1,92) |
|
|
>0,673 |
7 (87,5%) |
4 (50%) |
0,829 |
3,2 (0,52-19,43) |
||
|
stromal |
≤0,809 |
4 (50%) |
1 (12,5%) |
0,156 |
2,2
(0,89-5,39) |
|
|
>0,809 |
4 (50%) |
7 (87,5%) |
0,119 |
0,5
(0,19-1,11) |
||
|
NRP1 |
overall |
≤0,833 |
5 (62,5%) |
3 (37,5%) |
0,896 |
1,7 (0,59-4,73) |
|
>0,833 |
3 (37,5%) |
5 (62,5%) |
0,896 |
0,6 (0,21-1,70) |
||
|
parenchymal |
≤0,500 |
2 (25%) |
0 (0%) |
0,733 |
2,3 (01,27-4,27) |
|
|
>0,500 |
6 (75%) |
8 (100%) |
0,878 |
0,4 (0,23-0,79) |
||
|
stromal |
≤0,755 |
5 (62,5%) |
3 (37,5%) |
0,896 |
1,7 (0,59-4,73) |
|
|
>0,755 |
3 (37,5%) |
5 (62,5%) |
0,896 |
0,6 (0,21-1,70) |
||
|
MMP-2 |
overall |
≤0,024 |
7 (87,5%) |
3 (37,5%) |
0,296 |
4,2 (0,67-26,31) |
|
>0,024 |
1 (12,5%) |
5 (62,5%) |
0,209 |
0,2 (0,24-1,49) |
||
|
parenchymal |
≤0,010 |
8 (100%) |
5 (62,5%) |
0,100 |
- |
|
|
>0,010 |
0 (0%) |
3 (37,5%) |
0,0007 |
- |
||
|
stromal |
≤0,012 |
4 (50%) |
1 (12,5%) |
0,089 |
2,2 (0,89-5,39) |
|
|
>0,012 |
4 (50%) |
7 (87,5%) |
0,061 |
0,5 (0,19-1,11) |
||
|
MMP-9 |
overall |
≤0,336 |
1 (12,5%) |
4 (50%) |
0,334 |
0,3
(0,05-1,92) |
|
>0,336 |
7 (87,5%) |
4 (50%) |
0,234 |
3,2
(0,52-19,43) |
||
|
parenchymal |
≤0,305 |
0 (0%) |
2 (25%) |
0,733 |
- |
|
|
>0,305 |
8 (100%) |
6 (75%) |
0,549 |
- |
||
|
stromal |
≤0,157 |
0 (0%) |
2 (25%) |
0,733 |
- |
|
|
>0,157 |
8 (100%) |
6 (75%) |
0,639 |
- |
||
|
TGF-β |
overall |
≤0,923 |
3 (37,5%) |
7 (87,5%) |
0,336 |
0,4 (0,13-9,99) |
|
>0,923 |
5 (62,5%) |
1 (12,5%) |
0,254 |
2,8 (1,01-7,64) |
||
|
parenchymal |
≤0,940 |
3 (37,5%) |
8 (100%) |
0,05 |
0,3
(0,10-0,72) |
|
|
>0,940 |
5 (62,5%) |
0 (0%) |
0,045 |
3,7
(1,39-9,63) |
||
|
stromal |
≤0,498 |
1 (12,5%) |
3 (37,5%) |
0,335 |
0,4 (0,07-2,50) |
|
|
>0,498 |
7 (87,5%) |
5 (62,5%) |
0,661 |
2,3 (0,40-13,61) |
||
|
Erk2 |
overall |
≤0,003 |
4 (50%) |
3 (37,5%) |
0,988 |
1,3 (0,49-3,39) |
|
>0,003 |
4 (50%) |
5 (62,5%) |
0,201 |
0,8 (0,29-2,06) |
||
|
parenchymal |
≤0,001 |
3 (37,5%) |
1 (12,5%) |
0,667 |
1,8 (0,75-4,33) |
|
|
>0,001 |
5 (62,5%) |
7 (87,5%) |
0,361 |
0,6 (0,23-1,34) |
||
|
stromal |
≤0,0006 |
2 (25%) |
1 (12,5%) |
0,789 |
1,4 (0,54-3,89) |
|
|
>0,0006 |
6 (75%) |
7 (87,5%) |
0,536 |
0,7 (0,26-1,87) |
||
|
iNOS |
overall |
≤0,840 |
3 (37,5%) |
5 (62,5%) |
0,889 |
0,6 (0,21-1,70) |
|
>0,840 |
5 (62,5%) |
3 (37,5%) |
0,597 |
1,7 (0,59-4,73) |
||
|
parenchymal |
≤0,680 |
1 (12,5%) |
4 (50%) |
0,156 |
0,3 (0,05-1,92) |
|
|
>0,680 |
7 (87,5%) |
4 (50%) |
0,161 |
3,2 (0,52-19,43) |
||
|
stromal |
≤0,740 |
1 (12,5%) |
6 (75%) |
0,052 |
0,2 (0,03-1,17) |
|
|
>0,740 |
7 (87,5%) |
2 (25%) |
0,046 |
5,4 (0,86-34,56) |
||
As can be seen from the
table, a risk factor for poor outcome in patients with HGA of the colon is
overexpression of TGF-β (> 0,940) in
the parenchymal component of the tumor (RR (95% CI) = 3.7 (1,39-9,63), p =
0.045).
No statistically significant
differences in the expression of the other markers of angiogenesis have been
identified.
Conclusion: The risk factor of adverse outcome in patients with HGA of the
colon is overexpression of TGF-β (> 0,940) in
the parenchymal component of the tumor (RR (95% CI) = 3.7 (1,39-9,63), p =
0.045).
Literature:
1.
Штабинская,
Т.Т. Прогностическое значение уровня экспрессии фактора роста эндотелия сосудов
в колоректальном раке / Т.Т. Штабинская [и др.] // Научно-практический журнал
УО «Гродненский государственный медицинский университет». – 2015. - № 3(51). -
С. 64-69.