. .
. .
є
. .
-:
-,
-,
-,
-.
Н : 23.06.2009
П я : 03.08.2009
618.19-006.66:57.086.12:57.086.14
Ь
Е
Е Е
Д я - „І я
-я я я
-” (№ є
0101U001002).
.
, є є .
(ER, PgR,
HER-2/neu, pS2, 53, VEGF, -67, bcl-2)
, ’
. ( χ2),
. ER PgR
35 , ER – 35-50 . ER
PgR : ER
35-50 50 , 35 50
; PgR – 35-50 50 . 53 67
, є
-. є 35
. ’ є , є
/ .
. – 2009. – . , № 3. – . 154-162.
© . . , . . є , . . , 2009
Shponka I.S., Bondareva V.A., Shponka V.I. Immunohistochemical profile in estimation of biological properties and prognosis of breast cancer.
Summary. The prognostic value of markers of biological properties of breast cancer (BC), their age-dependent and mutual correlations are finally not determined. The purpose of our study was to determine the dependence of expression of prognos-tic markers (ER, PgR, HER-2/neu, pS2, 53, VEGF, -67, bcl-2) on age and presence of metastases at BC in women, to find the cross-correlations in groups with and without metastases. From data of statistical analysis (criterion of χ2), all of markers are thought to be used as prognostic of metastasis risk with the high level of reliability at patients of different age. The excep-tions were ER and PgR in group before 35 years, ER - in group 35-50 years. Only for the ER and PgR an increase of expres-sion with age was observed: for expresexpres-sion of ER a difference was reliable in groups 35-50 and above 50 years, in groups before 35 years and after 50 years; for PgR - between groups 35-50 years and above 50 years. The expression of markers of 53 and -67 showed the reliable difference in groups with the presence of metastases, regardless of age. The last are most reliable as prognostic for the group before 35 years. Cross-correlations between expression of markers which depended on age and/or metastasis were determined.
Key words: mammarygland, malignant tumors of epithelial origin, immunohistochemicalmarkers, prognosis.
( ) є
(
26%),
-є є
.
-є ,
.
(El Saghir N.S. et al.
2006; Bal W. et al., 2008), є
(Offersen B.V. et al., 2008),
pS2 (Ioakim-Liossi A. et al.,
1997), є
-:
–
(Offersen B.V. et al., 2008),
(VEGF), ,
:
bcl-2 (Ioachim E.E.
et al., 2000);
Ki-67 (Gerson R. et al., 2005).
-є
-є є
,
(Jang J.E. et al.,1999; Eppenberger-Castori S. et al., 2002; Al-Harris E.S., 2008).
,
’
.
-- 1305
.
-.
-.
4-6
SuperFrost Plus,
-.
-( ) (HІER – heat nduct on of
ep tope retr eval)
=6,0 (8
+1210 ).
(І )
-,
p53 ( DO-7 (DAKO), SP5
(LabVision)), Ki-67 (
MIB-1 (DAKO), SP6 (LabVision)), bcl-2
( 124 (DAKO), 100/D5 (LabVision)),
c-erbB-2/HER-2/neu (DAKO, SP3 (LabVision)),
: ER ( 1D5
(DAKO), SP1 (LabVision)) PgR ( PgR
636 (DAKO), SP2 (LabVision)), VEGF –
( VG1 (DAKO),
S2- ( BC04 (DAKO)). І
23-250
30 .
-.
LSAB2, EnVision
(DAKO) UltraVision LP (LabVision),
DAB
20 3 .
є .
-χ2
( - ), є є Exel.
(
-) 35
35-50 , 35
50 , 35-50
50 .
-’ є
’ ( . ., 1970 ),
-.
є 35
47,0% .
(33,4%).
40,5% ( . 1).
1
ER
І І І І
-,
- + ++ +++ - + ++ +++
11 5 4 5 14 2 5 5 11 14 14 12 < 35
(n=51)
25 26 112 36 59 66 52 28 35 22
112 161 52 85 35-50
(n=410)
273 137 126 71 84 221 86 60 89 107
126 376 86 256 > 50
(n=844)
ER+ ( .1) 69,3% .
є 35 ER+
51,0% .
, ER+
-.
(60,0%)
ER+ , . ER
( . 2) 41%
(Mts-) 37,9% –
(Mts+).
-,
-. 50
ER
(74,8%).
(p<0,001). , ’ ,
ER+
є
ER
. ER+
35 35-50 ,
35-50 50 , 35
50 (p<0,001
p<0,01 ).
. 1. І І Х я ER
МЗ 57 . ×400.
PgR+ ( . 3) 57,2% ( .
2).
-, PgR+ 43,1% .
PgR+
34,6% , – 52,0%.
є
51,5% PgR+ .
55,8% ,
43,1% .
PgR
-, PgR+
(p<0,05).
PgR+ 60,3%
є .
56,1% 63,1% .
PgR
35-50 50
(p<0,05).
. 2. ьІ Х ER
МЗ 40 ,
ь – МЗ. ×200.
. 3. І Х я
PgR МЗ 52
. ×400.
HER-2/neu 24,4%
( . 3).
(+++) 18,1% .
35 HER-2/neu
( . 4) 31,4%.
HER-2/neu
42,3%,
– 20,0% (p>0,05).
, ,
39,4%, – 16,8%
( <0,001). 50
HER-2/neu 23,9%.
17,1% .
31,3% ,
– 18,9% ( <0,001).
2
PgR
І І І І
,
- + ++ +++ - + ++ +++
12 2 5 6 17 3 4 2
12 13 17 9
< 35 (n=51)
25 26 121 34 68 50 78 21 26 12
121 152 78 59
35-50 (n=410)
273 137
185 73 138 106 150 69 83 40
185 317 150 192 > 50
(n=844)
502 342
3
HER-2/neu
І І І І
,
- + ++ +++ - + ++ +++
11 9 2 3 7 8 4 7 20 5 15 11 < 35
(n=51)
25 26 142 85 10 36 50 33 11 43
227 46 83 54
35-50 (n=410)
273 137 297 110 39 56 117 118 19 88
407 95 235 107 > 50
(n=844)
502 342
. 4. І І Х я (3+)
c-erbB-2/HER-2/neu МЗ
34 (×400).
VEGF-55,8% ( . 4).
58,8%.
55,1% , –
55,9%. 35 , VEGF+
65,4% 52,0% –
( >0,05).
VEGF+
59,9%
-, 52,7% – (p<0,01).
є 50 ,
-,
58,8%
54,0% (p<0,001).
53+ ( . 5)
26,3% ( . 5).
33,3%, – 28,0%, –
25,0%, (
4
VEGF
І І І І
,
- + ++ +++ - + ++ +++
6 6 9 4 3 6 9 8
12 13 9 17
< 35 (n=51)
25 26 73 56 95 49 16 39 46 36
129 144 55 82
35-50 (n=410)
273 137 155 76 175 96 54 87 125 76
231 271 141 201 > 50
(n=844)
502 342
5
53
І І І І
,
- + - + 20 5 14 12 < 35
(n=51) 25 26
221 52 74 63
35-50
(n=410) 273 137
425 77 208 134 > 50
(n=844) 502 342
. 5. І Х я 53
МЗ 45 . ×400.
35 p53+
46,2%
20,0% – ( <0,05). є
p53+
46,0%
19,0% – ( <0,001).
-є 50 p53+
39,2%
15,4% –
( <0,001).
bcl-2+ 50,3%
( . 6).
51,0% , – 51,2%, –
49,9%, є
.
є 35 bcl-2+
( . 6) 46,2%
56,0% –
( >0,05). bcl-2+
42,3%
, 55,7% –
( <0,05). є , 50 ,
bcl-2+ 44,2%
, – 53,8%
(p<0,01).
, -67
( . 7) , 10%,
20,4%, 10-20%
– 31,0%, -67
-, 20% – 48,6% ( . 7).
--67
36,0% 73% –
. -67
( <0,05).
68,5% ,
-, .
( <0,001).
-67 33,9%
69,9% – ( <0,001).
. 6. І Х я
bcl-2 МЗ 63 . ×400.
. 7. І Х я
Ki-67 МЗ 39 (×400).
Ч 47%.
pS2
( . 8) 52,9% ( . 8).
47,0%, –
55,9%, – 51,8%, є
.
6
bcl-2
І І І І
,
- + - + 11 14 14 12 < 35
(n=51) 25 26
121 152 79 58
35-50
(n=410) 273 137
232 270 191 151 > 50
(n=844) 502 342
7
Ki-67
(%) (%)
,
<10 10-20 >20 <10 10-20 >20 8 8 9 3 4 19 < 35
(n=51) 25 26
80 89 104 12 31 94 35-50
(n=410) 273 137
137 195 170 26 77 239
> 50
(n=844) 502 342
8
pS2
І І І І
,
- + - + 11 14 16 10 < 35
(n=51) 25 26
104 169 77 60
35-50
(n=410) 273 137
221 281 186 156 > 50
. 8. І Х я
pS2 МЗ 48 . ×400.
pS2+
-, ,
. ,
35 , pS2+ 56%
38,5% –
( <0,05).
pS2+ 43,8%
, 61,9% –
( <0,001). є , 50
, pS2+ 45,6%
-, – 55,9% ( <0,001).
2/neu, VEGF,
HER-2/neu, pS2, 53, 67, bcl-2
-.
’ є PgR
Bcl-2 (0,7Bcl-2, p<0,001), PgR pSBcl-2 (0,80, p<0,001), -’
є ER PgR (0,60, p<0,001), ER pS2 (0,62, p<0,001), ER Bcl-2 (0,41, p<0,001),
’
є Ki-67 53, Ki-67 VEGF, VEGF
53, Bcl-2 pS2.
'
-є ER Ki-67 0,40, p<0,001), PgR Ki-67 (-0,54, p<0,001), PgR VEGF (-0,48, p<0,001), Ki-67 Bcl-2 (-0,45, p<0,001), Ki-67 pS2 (-0,51 p<0,001), 53 pS2 (-0,44, p<0,001),
' є ER
HER-2/neu, PgR HER-HER-2/neu, ER 53, PgR 53,
HER-2/neu pS2, VEGF pS2, VEGF Bcl-2.
’
-є 53 HER-2/neu, 67 2/neu,
HER-2/neu bcl-2, HER-HER-2/neu VEGF.
’ ,
, ’ ,
-.
’ ,
(Ioachim E.E. et al.,
2000; Bartley A. N., Ross D. W., 2002; Li B.J. et al.,
2004; Gerson R. et al., 2009). ,
,
-є ,
-’ (Jang J.E. et
al., 1999; Al-Harris E.S. et al., 2008).
-, ’
:
1. ’ , є
-:
є VEGF p53 (0,25, p<0,001,
Mts-; 0,46, p<0,001, Mts+), Ki-67 p53
(0,07, p<0,05, Mts-; 0,33, p<0,001,
Mts+); bcl-2 pS2 (0,36, p<0,001, Mts-;
0,21, p<0,001, Mts+); ER VEGF (-0,30,
p<0,001, Mts-; -0,44, p<0,001,
Mts+), PgR VEGF (0,68, p<0,001, Mts-;
0,47, p<0,001, Mts+), p53 pS2 (-0,34,
p<0,001, Mts-; -0,55, p<0,001,
Mts+). є
-,
-.
;
, ,
-, .
2. ’ , є
( ): ER
53, PgR 53, 53 bcl-2 (
-’
); ER bcl-2, PgR
bcl-2 ( ’
); Ki-67 VEGF (
-’
-); pS2 HER-2/neu, pS2
VEGF ( ’
); pS2 Ki-67 (
-’
-).
3. ’ ,
-, є : PgR
pS2 (
’ ).
4. ’ ,
-, :
ER PgR, ER pS2 ( є
-’
-,
-є ); ER HER-2/neu, PgR
HER-2/neu ( є
’ ,
є
5. ’ : 53
HER-2/neu, 67 HER-2/neu HER-2/neu bcl-2,
HER-2/neu VEGF. ,
HER-2/neu .
( )
.
p<0,001
ER, PgR, HER-2/neu, pS2, 53, VEGF, 67,
p<0,01 – bcl-2.
, ER PgR
35 , ER -
35-50 . ER
PgR
: ER
35-50 50
(p<0,001), 35 50
(p<0,01); PgR – 35-50
50 (p<0,05). 53 67
,
є ,
. є
35 .
’ є
-, є
, – VEGF
p53, Ki-67 p53; bcl-2 pS2; ER VEGF, PgR VEGF, p53 pS2.
є є ’
є ER 2/neu, PgR
HER-2/neu ( ’
,
є
); ER 67, PgR 67, (
-’
-), ER PgR, ER pS2
( ’
,
-є ).
-є
-’ ER
53, PgR 53, 53 VEGF. ,
-є ,
, є .
-’
HER-2/neu.
’
-є 35-50 .
-.
. . : 2- . / .
. . – . : -
-, 1970. – 367 .
A comparison among HER2, TP53, PAI-1, an-giogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer / Birgitte Vrou Offersen, Jan Alsner, Karen Ege Olsen [et al.] // Acta Onc. – 2008. - Vol. 47. – P. 618-632.
Age-associated biomarker profiles of human breast cancer / Serenella Eppenberger-Castori, Dan H. Moore, Ann D. Thor [et al.] // Int. J. Bioch. & Cell Biol. – 2002. - Vol. 34, № 11. – P. 127-132.
Bartley A. N. Validation of p53 immunohisto-chemistry as a prognostic factor in breast cancer in clinical practice / Angela N. Bartley, Dennis W. Ross, // Arch. Path. Lab. Med. – 2002. - Vol. 126, № 4. - P. 456–458.
Breast cancer in young women (<35 years) : the impact of age on the prognosis / W. Bal, M. Jarzab, E. Nowara [et al.] // J. Clin. Oncol. – 2008. – Vol. 26. – P. 619.
Correlation between VEGF expression and prognostic factors in breast cancer / J. E. Jang, S.-Y. Choi, C. H. Park [et al.] // J. Korean Cancer Assos. - 1999. - Vol. 31, № 3. - P. 483-491.
Effects of young age at presentation on survival in breast cancer / Nagi S. El Saghir, Muhieddine Seoud, Mazen K. Khalil [et al.] // BMC Cancer. - 2006. - Vol. 6. – P. 194.
Expression correlation of Ki67 to P53,VEGF, and C-erbB-2 genes in breast cancer and their clini-cal significances / B. J. Li, Z. H. Zhu, J. Y. Wang [et al.] // Ai Zheng. – 2004. - Vol. 23, № 10. – P. 1176-1179.
Expression of pS2 protein and estrogen and progesterone receptor status in breast cancer / Anna Ioakim-Liossi, Petros Karakitsos, Christos Markopoulos [et al.] // Acta Cytol. – 1997. - Vol. 41. – P. 713-716.
Immunohistochemical expression of Bcl-2 pro-tein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices / Ioachim Elli E., Malamou-Mitsi Vasiliki, Kamina Sebasti A. [et al.] // Anticancer Res. – 2000. - Vol. 20, № 6. – P. 4221-4225.
KI67 in breast cancer: correlation between pro-liferation cellular and other prognostic factors / R. Gerson, L. Alban, A. Martínez [et al.] // J. Clin. On-col. – 2009. - Vol. 27. – P. 86-92.
breast cancer / E. S. Al-Harris, A. A. Al-Janabi, K. M. Al-Toriahi, A. A. Yasseen // Saudi Med. J. –
2008. – Vol. 29, № 8. – P. 1099-1104.
. ., . ., . .
.
. ,
.
(ER, PgR, HER-2/neu, pS2,
53, VEGF, -67, bcl-2) ,
.
( χ2),
.
ER PgR 35 , ER – 35-50 .
ER PgR : ER
35-50 50 , 35 50 ; PgR –
35-50 50 . , 53 -67
.
35 .
-, / .
: , ,
