Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers
Aim: To study the expression of estrogen receptors (ER) and progesterone receptors (PR) and proliferation marker Ki-67 in ovarian tumors using immunohistochemistry, and evaluate possible prognostic significance ofthese markers. Methods: Immunohistochemical evaluation of Ki-67, ER and PR expression...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Цитувати: | Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers / L.G. Buchynska, N.P. Iurchenko, V.M. Grinkevych, I.P. Nesina, S.V. Chekhun, V.S. Svintsitsky // Experimental Oncology. — 2009. — Т. 31, № 1. — С. 48-51. — Бібліогр.: 21 назв. — англ. |
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irk-123456789-1349302018-06-15T03:03:22Z Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers Buchynska, L.G. Iurchenko, N.P. Grinkevych, V.M. Nesina, I.P. Chekhun, S.V. Svintsitsky, V.S. Original contributions Aim: To study the expression of estrogen receptors (ER) and progesterone receptors (PR) and proliferation marker Ki-67 in ovarian tumors using immunohistochemistry, and evaluate possible prognostic significance ofthese markers. Methods: Immunohistochemical evaluation of Ki-67, ER and PR expression was performed on serous ovarian cancer (OC) tissue samples from 81 OC patients. Results: Serous OC is characterised by high proliferative activity and increased expression of steroid hormone receptors compared to nontransfomed ovarian surface epithelium. It has been shown that ER and PR expression levels depend on tumor histologic grade and the stage of the disease, and are variable between tumors of the same grade. The ER and PR expression levels correlate with OC patients’ survival. Conclusion: Proliferative activity and steroid hormone receptor status along with clinical and morphological characteristics of serous OC possess prognostic significance and may be used for evaluation of the disease course 2009 Article Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers / L.G. Buchynska, N.P. Iurchenko, V.M. Grinkevych, I.P. Nesina, S.V. Chekhun, V.S. Svintsitsky // Experimental Oncology. — 2009. — Т. 31, № 1. — С. 48-51. — Бібліогр.: 21 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/134930 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
| language |
English |
| topic |
Original contributions Original contributions |
| spellingShingle |
Original contributions Original contributions Buchynska, L.G. Iurchenko, N.P. Grinkevych, V.M. Nesina, I.P. Chekhun, S.V. Svintsitsky, V.S. Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers Experimental Oncology |
| description |
Aim: To study the expression of estrogen receptors (ER) and progesterone receptors (PR) and proliferation marker Ki-67 in ovarian
tumors using immunohistochemistry, and evaluate possible prognostic significance ofthese markers. Methods: Immunohistochemical
evaluation of Ki-67, ER and PR expression was performed on serous ovarian cancer (OC) tissue samples from 81 OC patients.
Results: Serous OC is characterised by high proliferative activity and increased expression of steroid hormone receptors compared
to nontransfomed ovarian surface epithelium. It has been shown that ER and PR expression levels depend on tumor histologic grade
and the stage of the disease, and are variable between tumors of the same grade. The ER and PR expression levels correlate with
OC patients’ survival. Conclusion: Proliferative activity and steroid hormone receptor status along with clinical and morphological
characteristics of serous OC possess prognostic significance and may be used for evaluation of the disease course |
| format |
Article |
| author |
Buchynska, L.G. Iurchenko, N.P. Grinkevych, V.M. Nesina, I.P. Chekhun, S.V. Svintsitsky, V.S. |
| author_facet |
Buchynska, L.G. Iurchenko, N.P. Grinkevych, V.M. Nesina, I.P. Chekhun, S.V. Svintsitsky, V.S. |
| author_sort |
Buchynska, L.G. |
| title |
Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers |
| title_short |
Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers |
| title_full |
Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers |
| title_fullStr |
Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers |
| title_full_unstemmed |
Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers |
| title_sort |
expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2009 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/134930 |
| citation_txt |
Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers / L.G. Buchynska, N.P. Iurchenko, V.M. Grinkevych, I.P. Nesina, S.V. Chekhun, V.S. Svintsitsky // Experimental Oncology. — 2009. — Т. 31, № 1. — С. 48-51. — Бібліогр.: 21 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT buchynskalg expressionoftheestrogenandprogesteronereceptorsasprognosticfactorinserousovariancancers AT iurchenkonp expressionoftheestrogenandprogesteronereceptorsasprognosticfactorinserousovariancancers AT grinkevychvm expressionoftheestrogenandprogesteronereceptorsasprognosticfactorinserousovariancancers AT nesinaip expressionoftheestrogenandprogesteronereceptorsasprognosticfactorinserousovariancancers AT chekhunsv expressionoftheestrogenandprogesteronereceptorsasprognosticfactorinserousovariancancers AT svintsitskyvs expressionoftheestrogenandprogesteronereceptorsasprognosticfactorinserousovariancancers |
| first_indexed |
2025-07-09T22:24:40Z |
| last_indexed |
2025-07-09T22:24:40Z |
| _version_ |
1837209887096963072 |
| fulltext |
48 Experimental Oncology 31, 48–51, 2009 (March)
Ovarian cancer (OC) is one of the most aggressive
malignancies of female reproductive system, occupy
ing the fourth place in the structure of cancer incidence
among Ukrainian women (14.3 per 100 000 women).
It has one of the highest levels among genital cancer
patients in Ukraine and other countries as well [1].
High mortality in OC patients is caused by the fact that
75% of OC cases are diagnosed at ІІІ–ІV stage, resul
ting in poor prognosis of the disease and low efficacy
of treatment [2].
OC pathogenesis and ethiology are still poorly un
derstood. Nevertheless, there are several hypothesis
of the pathology origin. Consistent with one of them,
the ovarian cancer occurrence is caused by a high
number of ovulations that leads to enforced prolife
ration of the ovarian surface epithelium, that fills the
wound defect arising from follicule rupture. So, the
number of ovulation cycles during lifetime is an indica
tor of the OC risk [2, 3].
Meanwhile, viral infection (by human papilloma
virus, for example, strains 16, 18, 48, 56) of the ovarian
epithelium contributes to OC development, especially
in case of serous neoplasia [4].
Moreover, genetic factors play an important part
in OC occurrence. Accumulation of genetic alterations
has been reported to underlie progressive transfor
mation of ovarian benign tumors into malignant ones
[5]. Numerous oncogenes and suppressor genes
determine ovarian tumors pathogenesis and progres
sion (acquisition of more malignant features during
tumor growth). Sporadic OC often carry mutations
in ТР53 tumor suppressor gene (in 50% of serous
adenocarcinomas, for example). Epithelial ovarian
tumors are characterized by changes in expression
of a number of cell cycle regulators, such as р16INK4a
(in 35% of OC cases), СDК4, cyclin D and Rb (retino
blastoma gene) (in 30% of OC cases), and overexpres
sion of HER2/neu oncogene (in 10–50% cases) [6].
A body of experimental, epidemiological and
clinical studies allows to characterize OC as a hormone
dependent tumor. By other words, an essential factor
in OC pathogenesis is hormonal imbalance determined
by an increase of pituitary gonadotrophic function,
resulting in ovulation overstimulation and chronic
hyperestrogenia along with a decrease in progester
one secretion. Hyperestrogenia can be considered
as an additional risk factor of ovarian malignancy [2].
More evidence on OC hormonedependence was
presented when estrogens (ER) and progesterone re
ceptors (PR) were detected. It was shown that ovaries
produce sex steroid hormones, and they are a target
of their action simultaneously; i. e. realization of hor
monal stimuli requires an adequate quantity of the recep
tors. Ovarian neoplasias are characterized by changes
in their receptor status, and, consequently, tumors can
be either primary receptornegative or as a result of their
progression they may lost the receptors.
In a number of studies it was shown that both mis
sense and nonsense mutations (resulting in complete
loss of expression) in ER genes are common in OC [7].
Steroid hormone receptors are a significant link
in hormonal signal transduction. They modulate such
important events, as cell differentiation, proliferation and
death through interaction with the respective ligands.
ER and PR levels depend on tumor histologic type,
patients’ age that determines their responsiveness
to hormonal therapy with synthetic progestagen and
antiestrogen [8].
It was noticed that receptor status and prolifera
tive activity determine tumor malignancy and disease
course [9–12]. However, no consensus on prognostic
EXPRESSION OF THE ESTROGEN AND PROGESTERONE RECEPTORS
AS PROGNOSTIC FACTOR IN SEROUS OVARIAN CANCERS
L.G. Buchynska1, *, N.P. Iurchenko1, V.M. Grinkevych2, I.P. Nesina1, S.V. Chekhun2, V.S. Svintsitsky3
1R.E.Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv
03022, Ukraine
2O.O.Bogomoletz National Medical University, Kyiv 01601, Ukraine
3PI “National Institute of Cancer”, Ministry of Health of Ukraine, Kyiv 03022, Ukraine
Aim: To study the expression of estrogen receptors (ER) and progesterone receptors (PR) and proliferation marker Ki-67 in ovarian
tumors using immunohistochemistry, and evaluate possible prognostic significance of these markers. Methods: Immunohistochemi-
cal evaluation of Ki-67, ER and PR expression was performed on serous ovarian cancer (OC) tissue samples from 81 OC patients.
Results: Serous OC is characterised by high proliferative activity and increased expression of steroid hormone receptors compared
to nontransfomed ovarian surface epithelium. It has been shown that ER and PR expression levels depend on tumor histologic grade
and the stage of the disease, and are variable between tumors of the same grade. The ER and PR expression levels correlate with
OC patients’ survival. Conclusion: Proliferative activity and steroid hormone receptor status along with clinical and morphological
characteristics of serous OC possess prognostic significance and may be used for evaluation of the disease course.
Key Words: ovarian adenocarcinoma, tumor grade, survival, Кі-67, estrogen and progesterone receptor expression.
Received: November 27, 2008.
*Correspondence: Fax: +38 (044) 258-16-56
E-mail: lubov@onconet.kiev.ua
Abbreviations used: ER — estrogen receptor; LI — labeling index;
OC — ovarian cancer; PR — progesterone receptor.
Exp Oncol 2009
31, 1, 48–51
Experimental Oncology 31, 48–51, 2009 (March) 49
significance of steroid hormone receptor expression
levels in ovarian tumors was reached yet.
Immunohistochemistry enables estimation of bio
markers expression in tumor tissue and determination
of morphological structures that express them [9, 13].
In the present paper we report the results of the
retrospective immunohistochemical investigation
of ER and PR expression and proliferative activity
in ovarian neoplasias and evaluation of their possible
prognostic significance.
MATERIALS AND METHODS
The current study was carried out on surgically resected
tumor samples (including archival ones) from 81 patients
with serous OC of І–IV stage (16–79 years old, average age
was 46.6 ± 2.4 years), 42 from which were at menstrual
period (16–55 years) and 39 — at menopausal period
(52–72 years). Morphologically not changed serous epi
thelium samples of endometrial fibromioma cases (n = 7)
were used as the relative negative control.
All patients underwent treatment in the Oncogyne
cological Department of the National Cancer Institute
of Ministry oh Health of Ukraine (headed by prof. Vorobyo
va) at the period from 1988 to 2005. The stage of tumor
process was determined according to FIGO classification
[14]. The data about disease clinical course, treatment
and patients’ outcome were obtained retrospectively from
each case history and ambulatory records. Accor ding
to these data, 20 patients survived for 5–17 years, and
for 29 patients survival period was < 5 years.
Immunohistochemistry on ER and PR expres
sion was performed on deparafinized slides, using
mouse monoclonal antibodies against ER (clone 1D5),
PR (clone PgR636) and Кі67 (clone МІВ1), and En
Vision visualization complex (DakoCytomation, Den
mark) according to manufacturer protocol [15]. Marker
expression was determined in 700–800 tumor cells.
The results of immunohistochemical reaction were
evaluated using semiquantitive method [15], using
calculation of positively stained cells or labelling in
dex (LI). ER and PR medians were 29.0% and 37.0%,
respectively. Consistent with these data, LI values less
and higher than median value Ме were considered
low and high, respectively. ER or PR expression was
considered negative when LI ≤ 10%.
Proliferation index (PI) was estimated as the number
of Ki67 expressing cells. Proliferation activity was con
sidered low if PI < 10.0%, and high if PI ≥ 10.0% [15].
Statistical analysis of obtained results was performed
using description statistic, the comparison of samples
(Mann — Whitney’s Utest), using program STATISTICA
6. Survival analysis was provided using Kaplan — Maier
method; statistical significance of the differences be
tween survival curves was defined by Coxtest [16–18].
RESULTS AND DISCUSSION
All studied neoplasias were diagnosed as serous
adenocarcinomas of different grade: G1 (n = 9), G2
(n = 34) or G3 (n = 38).
We have found that Ki67 was not expressed
in normal ovarian epithelial cells. At the same time,
the majority of serous tumors were highly prolifera
ting with PI ranging from 10 to 76.3% (average value
33.6 ± 2.8%). Analysis of steroid hormone recep
tors in all relative control samples has shown low
PR (14.2 ± 3.9%) and negative ER expression.
ER and PR expression in ovarian tumors increased
essentially, compared to that in the nontransformed
ovarian tissue, and was 29.0 ± 2.6% і 33.0 ± 3.1%,
respectively (Fig. 1, 2).
a
b
Fig. 1. High expression of estrogen receptors in ovarian cancer
cells. a, x 400; b, x 900
a
b
Fig. 2. High expression of progesterone receptors in ovarian
cancer cells. a, x 400; b, x 900
50 Experimental Oncology 31, 48–51, 2009 (March)
Positive expression was recorded almost in the
same number of OC cases: 68.0% of tumors was
PR positive, and in 67.0% of tumors ER positive. Mean
while, tumors with low ER and PR expression com
prised 25.5 and 15.0% of total OC cases. High expres
sion of these receptors was found in 42.0 and 53.0%
of total OC cases, respectively. Receptor’s phenotype
of neoplasm is one of the basic criteria of OC hormone
sensitivity; together with efficacy of hormonal therapy
it predetermines the prognosis of the disease.
The analysis of receptor phenotype of studied
ova rian tumors has shown that 54.0% of cases were
ER+PR+ positive, and in 21.0% of tumors both receptors
were not expressed. ER+PR– and ER–PR+ phenotypes
were determined in 14.0% and 11.0% of the patients.
The current study has demonstrated the relation
ship between the expression of steroid hormone recep
tors and the state of patients’ menstrual function. The
number of cells expressing ER in the group of patients
with a restored menstrual function was higher com
pared to this parameter in patients of menopausal age,
and were 30.0 ± 2.8% and 26.0 ± 2.4%, respectively.
For women at menopausal period PR expression was
reliably lower (27.0 ± 2.9%, р < 0.05) than for patients
with restored menstrual function (34.0 ± 3.2%).
The results of comparison of ER and PR expression
in І–ІІ and ІІІ–IV stage OC are shown in Table 1. It was
shown that a half of І–ІІ stage OC samples expresses
receptors versus 43.0% in ІІІ–IV stage OC samples.
Moreover, in the group of ІІІ–IV stage patients’ num
ber of receptornegative tumors was the three folds
increased.
Table 1. Steroid hormone receptor expression in ovarian adenocarcinomas
of different stages
Stage of disease
according to FIGO
Receptor expression profile, % of total case number
ER+PR+ ER+PR– ER–PR+ ER–PR–
І–ІІ 50.0 12.5 25.0 12.5
ІІІ–ІV 43.0 13.0 12.0 32.0
The investigation of ER and PR expression in ova
rian neoplasias of different grade has revealed signifi
cant heterogeneity of this index, especially in G2 and
G3 tumors (Table 2).
Table 2. ER and PR expression in ovarian neoplasias of different grade
Tumor histologic grade
Labelling index of the biomarker, %
ER
min–max
PR
min–max
G1 51.6 ± 4.6
29–70
51.8 ± 4.3
37–70
G2 31.8 ± 3.6
0–69
37.8 ± 4.7
0–84
G3 21.0 ± 3.9
0–90
24.2 ± 4.4
0–84
ER and PR expression was the highest in G1 tumors
and decreases along with disease progression reaching
its minimal values in G3 ovarian carcinomas (p < 0.005).
It should be noted that among patients with
G1 ovarian tumors, high ER and PR expression was
prevalent, while lower differentiation grade corre
sponds to higher numbers of cases with low or nega
tive receptors expression. ER and PR expression was
absent in 26.5% of G2 tumors, whereas there was
a 2fold increase in the number of such cases among
G3 carcinomas (Fig. 3).
ER
0
10
20
30
40
50
60
70
80
90
100
G1 G2 G3
Q
ua
nt
ity
o
f t
um
ou
rs
wi
th
E
R
ex
pr
es
si
on
, %
Negative
Low
High
PR
0
10
20
30
40
50
60
70
80
90
100
G1 G2 G3
Q
ua
nt
ity
o
f t
um
ou
rs
wi
th
P
R
ex
pr
es
si
on
, %
Negative
Low
High
a
b
Fig. 3. Distribution of ovarian serous adenocarcinomas of dif
ferent grade according to the level of steroid hormone receptor
expression
The study of receptor expression has revealed that all
G1 tumors were positive (ER+PR+ phenotype), while ova
rian carcinomas of higher grade showed an increase in the
number of receptor negative (ER–PR–) cases (Table 3).
Table 3. Steroid hormone receptor expression in ovarian adenocarcinomas
of different grade
Tumor histologic
grade
Receptor phenotype, %
ER+PR+ ER+PR– ER–PR+ ER–PR–
G1 100.0 – – –
G2 61.7 14.7 8.8 14.7
G3 36.8 15.8 15.8 31.6
In order to estimate the prognostic significance
of steroid hormone receptor expression, groups
of OC patients were standardized according to type
and regimen of applied polychemotherapy.
Based on analysis of survival curves of OC patients,
it was possible to determine the ER and PR expression
levels (29.0% and 37.0%) that were of critical pro
gnostic significance. We have found that 5year survival
of 75.0% and 65.0% was reliably higher in OC patients
with high levels of ER and PR expression (higher than
29.0% and 37.0%, respectively), compared to patients
with lower values of expression (Fig. 4).
Obtained data indicate that the expression of steroid
hormone receptors could be considered as an inde
pendent prognostic factor in ovarian neoplasias. This
hypothesis is supported by the number of female re
productive system malignancy studies, showing a great
importance of receptor status in hormonedependent
tumors. For example, Ellinidi et al. [19] have reported
on estrogenandprogesterone receptor phenotype
as an important prognostic parameter, reflecting the
presence of two pathogenetic pathways of breast
cancer development. Meanwhile, it was shown that
endometrial neoplasms that expreesed ER and PR were
Experimental Oncology 31, 48–51, 2009 (March) 51
characterised by low grade, insignificant depth of mio
metrium invasion, low number of metastases in re
gional lymph nodes and better survival, compared to the
negative cases. It is noteworthy, that the expression
of ER and PR is important for the course and outcome
of endometrial cancer [20]. However, for prognosis
of OC outcome PR expression is considered to be most
valuable [8, 9]. The prognostic significance of ER ex
pression is far from being completely determined, but
there is some evidence that the loss of estrogen recep
tor β promotes OC development [21].
0 20 40 60 80 100 120 140 160 180 200 220
Months
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
T
ot
al
s
ur
viv
in
g
ЕR < Me(29.0)
ЕR > Me(29.0)
5-year survival 75.0%
5-year survival 26.0%
0 20 40 60 80 100 120 140 160 180 200 220
Months
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
T
ot
al
s
ur
viv
in
g
PR < Me(37.0)
PR > Me(37.0)
5-year survival 65.0%
5-year survival 39.0%
Cox-Mantel Test
p = 0.0004
Cox-Mantel Test
p = 0.01326
a
b
Fig. 4. Survival curves for OC patients dependent on ER (a) and
PR (b) expression
In conclusion, the current study shows that serous
OC is characterised by high proliferative activity and
increased expression of steroid hormone receptors
compared to those in the nonchanged ovarian surface
epithelium. It was shown that ER and PR expression
depends on tumor histologic grade and varies between
the tumors of the same grade. The receptor phenotype
of serous ovarian tumors correlates with disease stage,
and level of steroid hormone receptor expression is one
of the significant factors that determine OC patients’ sur
vival. Proliferative activity and steroid hormone receptor
status along with clinical and morphological characteris
tics of the disease have prognostic significance and may
be used for evaluation of serous OC course.
REFERENCES
Fedorenko ZP, Gulak LO, Goroh YL, 1. et al. Cancer
in Ukraine, 2005–2006. Incidence, mortality indices of on
cologic service. The bulletin of Ukrainian National Cancer
Register, 2007; 9: 45 (in Ukrainian).
Urmancheeva AF, Meshkova IE. 2. Question of epidemio
logy and diagnostics of ovarian cancer. Prac Oncol 2000; 4:
7–13 (in Russian).
Mc Cluggage WG. 3. My approach to and thoughts on the
typing of ovarian carcinomas. J Clin Pathol 2008; 61: 152–6.
Giordano G, D’Adda T, Gnetti L, 4. et al. Role of human
papillomavirus in the development of epithelial ovarian neoplasms
in Italian women. J Obstet Gynaecol Res 2008; 34: 210–7.
De Sousa Damiăo R, Fujiyama Oshima CT, Stavele JN, 5.
et al. Analysis of the expression of estrogen receptor, proges
terone receptor and chicken ovalbumin upstream promoter
transcription factor I in ovarian epithelial cancers and normal
ovaries. Goncavels WJ Oncol Rep 2007; 18: 25–32.
Garcia-Velasco A, Mendiola C, Sanchez-Munoz A, 6.
et al. Prognostic value of hormonal receptors, p53, Ki67 and
HER2/neu expression in epithelial ovarian carcinoma. Clin
Transl Oncol 2008; 10: 367–71.
Chu S, Mamerrs P, Burger H, 7. et al. Estrogen receptor
isoform gene expression in ovarian stromal and epithelial
tumors. J Clin Endocrinol 2006; 85: 1200–05.
Smyth JF, Gourley Ch, Walker G, 8. et al. Antiestrogen
therapy is active in selected ovarian cancer cases: the use
of letrozole in estrogen receptorpositive patients. Clin Cancer
Res 2007; 13: 3617–22.
Pozharisky KM, Leenman EE. 9. Importance of immuno
histochemical methods for determination of cancer treatment
pattern and prognosis. Path Arch 2000; 5: 11–7 (in Russian).
Beenken SW, Bland KI. 10. Biomarkers for breast cancer.
Minerva Chir 2002; 57: 437–8.
Shupnik MA. 11. Estrogen receptorβ: why may it influ
ence clinical outcome in estrogen receptorβ positive breast
cancer? Breast Cancer Res 2007; 9: 107–8.
Conway K, Parrish E, Edmiston SN, Tolbert D, 12. et al. Risk
factors for breast cancer characterized by the estrogen receptor alpha
A908G (K303R) mutation. Breast Cancer Res 2007; 9: 36–46.
Bozhok AA, Semiglazov VF, Semiglasov VV, 13. et al. Pro
gnostic and predictive factors in breast cancer. Oncol Issues
2005; 51: 434–41 (in Russian).
Tavassoli FA, Develee P, eds. 14. Pathology and genetics
of tumours of the breast and female genital organs. Lyon:
IARC Press, 2003.
Buchynska LG, Nesina IP, Yurchenko NP, 15. et al.
Expression of p53, p21WAF1/CIP1, p16INK4a and Кi67 proteins
in serous ovarian tumors. Exp Oncol 2007; 29: 49–53.
Lapach SN, Gubenko AV, Babich PN. 16. Statistical me
thods in medical and biological investigations using Excel.
Kyiv: Morion, 2001 (in Russian).
Kaplan EL, Meier PN. 17. Nonparametric estimation from
incomplete observations. J Am Stat Assos 1958; 53: 457–81.
Glants С. 18. Medical and biological statistics. Moscow:
Practice, 1998 (in Russian).
Ellinidi VN, Anikeyeva NV, Goncharova OA, Kras-19.
nozhon DA. Comparative analysis of proliferation activity
in breast cancer with different estrogen and progesterone re
ceptor status. Oncology Issues 2005; 51: 197–9 (in Russian).
Berstein LM, Tsyrlina YV, Kovalenko IG, 20. et al. Study
of hormonemetabolitic status in patients with receptor
negative tumours of the breast and endometrium. Oncol Issues
2003; 49: 716–24 (in Russian).
Bardin A, Hoffman P, Bolee N, 21. et al. Involvement
of estrogen receptor β in ovarian carcinogenesis. Cancer Res
2004; 64: 5861–69.
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