A study of transferrin and ferritin expression in tumor cells of patients with breast cancer
Aim: to study and to evaluate the clinical significance of the expression of iron-containing proteins ferritin and transferrin in tumor cells of patients with breast cancer (BC). Object and methods: the study included 143 patients with BC stage II–III. Methods: clinical, morphological and immunoh...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2014
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nasplib_isofts_kiev_ua-123456789-1376242025-02-09T17:08:06Z A study of transferrin and ferritin expression in tumor cells of patients with breast cancer Дослідження експресії трансферину та феритину у пухлинних клітинах хворих на рак молочної залози Shepil, O.V. Lukyanova, N.Y. Chekhun, S.V. Polishchuk, L.Z. Antipova, S.V. Оригинальные исследования Aim: to study and to evaluate the clinical significance of the expression of iron-containing proteins ferritin and transferrin in tumor cells of patients with breast cancer (BC). Object and methods: the study included 143 patients with BC stage II–III. Methods: clinical, morphological and immunohistochemical, statistical. Results: it was shown that BC is characterized by intertumor heterogeneity of expression of transferrin and ferritin. The high degree of differentiation of BC correlates with the lack of expression of transferrin and ferritin. Positive expression of these proteins in the cells of primary tumors correlated with the development of metastases in regional lymphatic nodes. Correlation dependences between parameters of expression of transferrin and ferritin in tumor cells and overall survival in patients with BC have been determined. Conclusions: the expression of transferrin and ferritin may be individual predictive markers of clinical course and survival in patients with BC and one more molecular target for the development of new anticancer agents. Мета: вивчення експресії залізовмісних білків феритину (ФЕР) і трансферину (ТРФЕР) у пухлинних клітинах та оцінка її клінічного значення у хворих на рак молочної залози (РМЗ). Об’єкт і методи: у дослідження включено 143 пацієнток із РМЗ ІІ–ІІІ стадії. Методи дослідження: клінічні, морфологічний, імуногістохімічний, статистичний. Результати: показано, що РМЗ характеризується міжпухлинною гетерогенністю експресії ТРФЕР і ФЕР. Високий ступінь диференціювання РМЗ корелює з відсутністю експресії ТРФЕР і ФЕР. Позитивна експресія цих білків у клітинах первинної пухлини пов’язана з розвитком метастазів у регіонарних лімфатичних вузлах. Встановлено кореляційну залежність між експресією ТРФЕР та ФЕР у пухлинних клітинах і загальною виживаністю хворих на РМЗ. Висновки: експресія ТРФЕР і ФЕР може бути індивідуальним предиктивним маркером перебігу хвороби та виживаності пацієнток із РМЗ і ще однією молекулярною мішенню для розробки нових протипухлинних агентів. 2014 Article A study of transferrin and ferritin expression in tumor cells of patients with breast cancer / O.V. Shepil, N.Y. Lukyanova, S.V. Chekhun, L.Z. Polishchuk, S.V. Antipova // Онкологія. — 2014. — Т. 16, № 2. — С. 108-112. — Бібліогр.: 35 назв. — англ. https://nasplib.isofts.kiev.ua/handle/123456789/137624 en Онкологія application/pdf 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 |
| collection |
DSpace DC |
| language |
English |
| topic |
Оригинальные исследования Оригинальные исследования |
| spellingShingle |
Оригинальные исследования Оригинальные исследования Shepil, O.V. Lukyanova, N.Y. Chekhun, S.V. Polishchuk, L.Z. Antipova, S.V. A study of transferrin and ferritin expression in tumor cells of patients with breast cancer Онкологія |
| description |
Aim: to study and to evaluate the clinical significance of the expression
of iron-containing proteins ferritin and transferrin in tumor cells of patients with
breast cancer (BC). Object and methods: the study included 143 patients with BC
stage II–III. Methods: clinical, morphological and immunohistochemical, statistical.
Results: it was shown that BC is characterized by intertumor heterogeneity
of expression of transferrin and ferritin. The high degree of differentiation
of BC correlates with the lack of expression of transferrin and ferritin. Positive expression
of these proteins in the cells of primary tumors correlated with the development
of metastases in regional lymphatic nodes. Correlation dependences between
parameters of expression of transferrin and ferritin in tumor cells and overall
survival in patients with BC have been determined. Conclusions: the expression
of transferrin and ferritin may be individual predictive markers of clinical course
and survival in patients with BC and one more molecular target for the development
of new anticancer agents. |
| format |
Article |
| author |
Shepil, O.V. Lukyanova, N.Y. Chekhun, S.V. Polishchuk, L.Z. Antipova, S.V. |
| author_facet |
Shepil, O.V. Lukyanova, N.Y. Chekhun, S.V. Polishchuk, L.Z. Antipova, S.V. |
| author_sort |
Shepil, O.V. |
| title |
A study of transferrin and ferritin expression in tumor cells of patients with breast cancer |
| title_short |
A study of transferrin and ferritin expression in tumor cells of patients with breast cancer |
| title_full |
A study of transferrin and ferritin expression in tumor cells of patients with breast cancer |
| title_fullStr |
A study of transferrin and ferritin expression in tumor cells of patients with breast cancer |
| title_full_unstemmed |
A study of transferrin and ferritin expression in tumor cells of patients with breast cancer |
| title_sort |
study of transferrin and ferritin expression in tumor cells of patients with breast cancer |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2014 |
| topic_facet |
Оригинальные исследования |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/137624 |
| citation_txt |
A study of transferrin and ferritin expression in tumor cells of patients with breast cancer / O.V. Shepil, N.Y. Lukyanova, S.V. Chekhun, L.Z. Polishchuk, S.V. Antipova // Онкологія. — 2014. — Т. 16, № 2. — С. 108-112. — Бібліогр.: 35 назв. — англ. |
| series |
Онкологія |
| work_keys_str_mv |
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2025-11-28T09:39:10Z |
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2025-11-28T09:39:10Z |
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ОНКОЛОГИЯ • Т. 16 • № 2 • 2014
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
108
INTRODUCTION
Ferritin (FER) and transferrin (TRFER) belong to
the iron-containing proteins involved in many physiolo-
gical and pathological processes. According to the data
of literature, iron-containing proteins play the main role
in control of iron homeostasis in organism as well as
in such biological processes as development of tissues,
functional activity of cells, angiogenesis, proliferation
and regu lation of cellular cycle, etc. [1–4]. Expression
of genes involved in iron metabolism, including genes
of TRFER, FER and ferroportin, is regulated by iron reg-
ulatory proteins 1/2 (IRP1/2) on the posttranscription-
al level [5, 6]. Interest in study of the role of iron-con-
taining proteins in cancer patients is conditioned by their
role in regulation of iron metabolism in the pre sence of
malignant neoplasm in organism [7, 8]. In series of stu-
dies, connections between changes in le vel of iron-con-
taining proteins and progression of tumor, as well as in-
creased DNA synthesis in tumor cells (TC), expression
of angiogenic factors (VEGF), reaction of cells to the ox-
idative stress, have been showed [9–11].
According to the results of numerous studies, FER is
a cytoplasmic protein playing key role in intracellular iron
homeostasis. At the same time, it can locate in cell nuclei,
including tumor nuclei. This protein has many functions,
particularly protection of cells from oxidative stress, re-
gulatory role in transcription processes, and preservation
of iron in bioactive and non-toxic forms [12–14]. Syn-
thesis of intracellular FER is controlled on transcrip-
tional and translational levels by two ways — iron-de-
pendent and iron-independent [14]. FER is also known
as proinflammatory mediator, expression of which can
by induced by cytokines; however, it can induce expres-
sion of both proinflammatory and antiinflammatory cy-
tokines and be immunosuppressant [15].
Another one iron-containing protein TRFER,
which main function consists in transfer and deli very
of iron to the cells, belongs to the markers of malig-
nant tumor phenotype, since it is associated with
proliferation of cells. It has been clearly demonstra-
ted by example of cancer and neuroendocrine car-
cinomas of pancreatic gland: the highest expression
of TRFER was in proliferating cells of both primary
tumors and metastases [16]. Number of TRFER re-
ceptors (TfR1 and TfR2-alpha) in proliferating cells
of hepatoma compared with cells in dormancy incre-
ases up to 300 and 200%, respectively [17]. Using com-
parative immunohistochemical (IHC) studies of ex-
pression of markers in tumor and normal cells, it has
been showed that level and distribution of TRFER re-
ceptor in tumors of other genesis (colorectal cancer)
changes depending on stage of tumor process and tu-
mor differentiation grade: high expression of TRFER
receptors in cells of highly differentiated forms of can-
cer at sta ges A and B by Dukes and lack/low expression
in cells of low differentiated carcinomas with metas-
tases at stage C or D [18]. Biological role of TRFER
at tumor growth is confirmed also in study, in which
was sta ted that TRFER receptors can have different
regulatory properties and differentially be expressed
in proli ferating cells compared with those being in
dormancy [19]. Although interest in iron-containing
proteins and their role in TC homeostasis significantly
increased in recent years, number of studies on FER
and TRFER in TC of mammary gland is insufficient.
Our previous in vitro studies have showed that
the most essential disorders of homeostasis of endoge-
nous iron and increased level of FER and TRFER ex-
pression are detected in TC of human mammary gland of
the most aggressive mesenchymal phenotype and in cells
A STUDy Of TRANSfERRIN
AND fERRITIN EXPRESSION
IN TUMOR CELLS Of PATIENTS
WITh bREAST CANCER
Summary. Aim: to study and to evaluate the clinical significance of the expression
of iron-containing proteins ferritin and transferrin in tumor cells of patients with
breast cancer (BC). Object and methods: the study included 143 patients with BC
stage II–III. Methods: clinical, morphological and immunohistochemical, sta-
tistical. Results: it was shown that BC is characterized by intertumor heteroge-
neity of expression of transferrin and ferritin. The high degree of differentiation
of BC correlates with the lack of expression of transferrin and ferritin. Positive ex-
pression of these proteins in the cells of primary tumors correlated with the deve-
lopment of metastases in regional lymphatic nodes. Correlation dependences be-
tween parameters of expression of transferrin and ferritin in tumor cells and over-
all survival in patients with BC have been determined. Conclusions: the expression
of transferrin and ferritin may be individual predictive markers of clinical course
and survival in patients with BC and one more molecular target for the develop-
ment of new anticancer agents.
O.V. Shepil1,2
N.Y. Lukyanova2
S.V. Chekhun2
L.Z. Polishchuk2
S.V. Antipova3
1Lugansk Regional Clinical
Oncology Dispensary, Lugansk
2R.E. Kavetsky Institute
of Experimental Pathology,
Oncology and Radiobiology
of NAS of Ukraine, Kyiv
3Lugansk State Medical
University, Lugansk, Ukraine
Key words: breast cancer,
transferrin, ferritin, prognosis.
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
109ОНКОЛОГИЯ • Т. 16 • № 2 • 2014 109
with phenotype of treatment resistance to the antitumor
drugs of different mechanism of action [20, 21]. Also,
we have determined connection between FER level in
blood serum and tumor tissue and sensitivity to neoadju-
vant the rapy in patients with breast cancer (BC) [22, 23].
However, to date there is no consensus of opinion con-
cerning significance of presence of these proteins for
prognosis of clinical course and survival of BC patients.
Aim of the study was to investigate the expression
of iron-containing proteins FER and TRFER in TC
of BC patients and to evaluate their clinical significance.
ObjECT AND METhODS
Retrospective analysis of the results of examination,
treatment and survival of 143 BC patients of II–III stage,
who have been receiving inpatient treatment on the ba-
sis of Lugansk Regional Clinical Oncology Dispensary
during 2005–2010, has been carried out. Stage of tumor
process was determined according with the Internatio-
nal clinical classification of tumors (TNM, 6th edition,
2002). Histological type of removed tumors was verified
at morphological study of histological sections (staining
with hematoxylin and eosin) according with the WHO
International histological classification (2001). All pa-
tients underwent adjuvant polychemotherapy (PCT)
according with the standards of treatment approved in
Ukraine by FAC or AC schemes with 21 day interval,
number of PCT courses — 4–6. Postsurgical radiothe-
rapy (RT) was carried out on gamma-therapeutic equip-
ment «TERAGAM» (single focal dose 2 Gy, total focal
dose 40 Gy) on the area of postsurgical scar, inguinal,
parasternal and supraclavicular areas.
For IHC study of FER and TRFER expression in
TC, standard streptavidin-biotin-peroxidase me thod
was applied. As primary were used antibodies speci fic
to FER and TRFER (Abcam, USA). For visu alization
of the results of reaction, reagent kit EnVision System,
LSAB2 (Dako, Denmark) were used according with
manufacturer’s recommendations; histological sec-
tions were stained with Mayer hematoxylin. Evalua-
tion of the results was carried out using optic micros-
copy at magnification ×200. For evaluation of FER
and TRFER expression, semi-quantitative method was
applied. In each histological specimen, expression of
markers in 1000 TC was analyzed determining quanti-
ty of positive and negative cells in percentage and cal-
culating level of expression of marker (high, moderate,
strong). Strong positive expression of marker was con-
sidered quantity of positive TC > 10% and strong/mo-
derate expression of markers [24].
Statistical processing of the results of study was car-
ried out using methods of variation statistics with use
of program STATISTICA 6.0. For evaluation of signi-
ficance of differences in expression of studied markers
and other clinical-pathological parameters, χ2 was used.
Evaluation of survival was carried out by Kaplan — Me ier
me thod taking date of the beginning of treatment as re-
ference point. Multivariate analysis was performed using
Cox regression model and log-rank test. Correlation ana-
lysis was carried out by calculation of Spearman corre-
lation. Critical level of statistical significance was 0.05.
RESULTS AND DISCUSSION
General clinical characteristic of BC patients of II–
III stage is given in Table 1. Age of patients varied from
25 to 76, mean age — 50.3 ± 4.3. The highest (27.1%)
number of patients was in age interval 51–60. Most
(61.5%) patients were in menopause. Part of BC patients
of II stage has constituted 44.0%, III — 56.0%. Number
of women with BC of IIa and IIb stages was almost equal
and constituted 21.0 and 23.0%, respectively. Among pa-
tients with III stage T3a (33.1%) was prevailed; stage T3b
was detected in 22.9% of patients. In 22.4% of patients,
no metastases in lymph nodes (LN) were detected, in
77.6% metastatic involvement of LN was diagnosed.
Complex examination of patients (radiological, ultra-
sound, laboratory), which was carried out before treat-
ment, has not detected remote metastases. Morphologi-
cal study of surgical material has showed that infiltrating
duct cancer occurred more often (77.6%), than lobular
cancer (22.4%); moderate tumor differentiation grade
was determined in 42.6% of patients.
Total number of tumors with positive TRFER and
FER expression was the same in both groups and con-
stituted 75 (52.4%) and 74 (51.4%), respectively. Here-
after, TRFER and FER expression has been analyzed
depending on such clinical features, as stage of disease, his-
tological type of tumor and its differentiation grade, pre-
sence/lack of metastases of cancer in regional LN, over-
all survival (OS) of patients. No significant diffe rences
in frequency of positive (+) tumors depending on stage
and histological structure of BC was detected. In parti-
cular, TRFER+ tumors were detected in 37 (58.7%) pa-
tients with II stage and in 38 (60.3%) — with III stage;
FER+ — in 33 (52.3%) and 41 (51.2%) patients corre-
spondingly. TRFER+ were 57 (51.3%) samples of infil-
trating duct cancer and 18 (56.25%) — infiltrating lobular
cancer; FER+ — 58 (52.2%) and 16 (50%), respectively.
In group of patients with high and moderate BC dif-
ferentiation grade, number of tumors with positive ex-
pression of TRFER and FER was lesser, than in patients
with low differentiation grade (р < 0.05) (Table 2). Num-
ber of tumors with positive expression of both markers
turned out to be significantly higher (р < 0.05) in BC pa-
tients with metastases in LN (Table 3).
Results of correlation analysis are given in Table 4.
No correlation between TRFER and FER expression
and stage of BC and histological type of tumor has been
determined. Also, it has been determined that TRFER/
FER negative expression correlates with high differen-
tiation grade of tumors, and positive TRFER/FER ex-
pression in primary tumor — with development of me-
tastases in regional LN. No significant correlations be-
tween TRFER and FER expression in samples of one
tumor were detected (r = 0.10; p > 0.05) that points out
at different ways of regulation of these proteins, which
are quite complicated in TC, finally not determined and
need further study [25].
ОНКОЛОГИЯ • Т. 16 • № 2 • 2014
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
110
Table 1
General clinical characteristic of BC patients
Index Number of patients
n %
Total number of patients 143 100
Menstrual cycle
Preserved 55 38.5
Menopause 88 61.5
BC stage by TNM (category Т)
ІІ (Т2)
including Т2а
Т2b
63
48
15
44.0
21.0
23.0
III (Т3)
including Т3а
Т3b
80
62
18
56.0
33.1
22.9
Metastases in regional LN (category N)
N0 32 22.4
N1–3 111 77.6
Remote metastases (category М)
М0 143 100.0
BC morphology
Infiltrating duct cancer 111 77.6
Infiltrating lobular cancer 32 22.4
BC differentiation grade
High 40 28.0
Moderate 61 42.6
Low 42 29.4
Methods of treatment
Mastectomy by Madden + PCT 51 35.7
Mastectomy by Madden + PCT + RT 57 39.9
Mastectomy by Madden + RT 35 24.4
Table 2
Distribution of tumors by TRFER and FER expression depending
on BC differentiation grade
Differentiation grade
Nu
m
be
r o
f t
um
or
s
wi
th
p
os
iti
ve
ex
pr
es
si
on
o
f T
RF
ER
Nu
m
be
r o
f t
um
or
s
wi
th
n
eg
at
iv
e
ex
pr
es
si
on
o
f T
RF
ER
Nu
m
be
r o
f t
um
or
s
wi
th
p
os
iti
ve
ex
pr
es
si
on
o
f F
ER
Nu
m
be
r o
f t
um
or
s
wi
th
n
eg
at
iv
e
ex
pr
es
si
on
o
f F
ER
n % n % n % n %
High
(n = 40/100.0%) 19 47.5 21 52.5 16 40.0 24 60.0
Moderate
(n = 61/100.0%) 21 34.4 40 65.6 24 39.3 37 40.7
Low
(n = 42/100.0%) 35 83.3 17 16.7 34 80.1 7 9.9
Total
(n = 143/100.0%) 75 52.4 68 47.6 74 51.4 69 48.6
Using Kaplan — Meier method, 5-year OS of patients
depending on TRFER and FER expression has been cal-
culated. As data in Fig. 1 and 2 show, survival of BC pa-
tients was higher at lack of TRFER and FER expression
in remote tumors. Cox regression analysis conducted for
determination of connections between TRFER and FER
expression and OS rates of patients has showed that these
proteins may be used as subsidiary predictive markers
of BC prognosis (for TRFER β = −0.44; p < 0.05; for
FER β = −0.29; p < 0.05).
When analyzing obtained results and summarizing
conducted study, one should mention that molecular
and clinical aspects of changes in iron homeostasis in
organism of patients and TC and their diagnostic va-
lue are characterized by complexity of signal path-
ways of expression of markers, which are connec ted
with iron metabolism [25]. Significance of disorders
of iron homeostasis for occurrence and progression of
cancer diseases, including BC, is confirmed by data
of numerous epidemiological and experimental stud-
ies [1, 26–28]. Mechanisms of these disorders to date
are not fully studied. There are data showing synergism
of disorders of iron and estrogen metabolism at occur-
rence of BC. In general, characteristic feature of TC
is increased expression of proteins-importers and de-
crease of level of proteins-exporters of iron [28]. Du-
ring the process of carcinogenesis, excess of iron con-
tributes to the formation of active oxy gen forms, which
cause DNA damages. At the same time, estrogen can
be additional substrate of these reactions due to attach-
ment of hydroxyl group and formation of catechol es-
trogen [28–30]. Compensatory protective mechanism,
which contributes to the neutralization of free radi-
cals and protection of DNA from damages caused by
excess of iron, is increasing of FER level in TC. Di-
sorders of estrogen metabolism on the background of
excess of iron also cause stimulation of TRFER syn-
thesis in TC of mammary gland. It is confirmed by ob-
tained by us data and results of previous studies [22],
which are the evidence of presence of increased level
of FER and TRFER expression in more than 50% of
studied tumors of mammary gland.
Table 3
Distribution of tumors by TRFER and FER expression depending
on presence of BC metastases in regional LN
Category N
Nu
m
be
r o
f t
um
or
s
wi
th
p
os
iti
ve
ex
pr
es
si
on
o
f T
RF
ER
Nu
m
be
r o
f t
um
or
s
wi
th
n
eg
at
iv
e
ex
pr
es
si
on
o
f T
RF
ER
Nu
m
be
r o
f t
um
or
s
wi
th
p
os
iti
ve
ex
pr
es
si
on
o
f F
ER
Nu
m
be
r o
f t
um
or
s
wi
th
n
eg
at
iv
e
ex
pr
es
si
on
o
f F
ER
n % n % n % n %
N0 (n = 32/100.0%) 9 28.1 23 71.9 11 34.4 21 65.6
N1–3 (n = 111/100.0%) 66 59.5 45 40.5 63 56.8 48 43.2
Total (n = 143/100.0%) 75 52.4 68 47.6 74 51.4 69 48.6
Table 4
Correlation of expression of studied molecular markers with clinical
and morphological features of BC
Correlation pairs Correlation
coefficient
Evaluation
of correlation
TRFER expression Stage of
disease
0.09 No correlation between
TRFER/FER expression
and stage of diseaseFER expression −0.02
TRFER expression Histologi-
cal type of
BC
0.06 No correlation between
TRFER/FER expression
and histological type
of tumor
FER expression 0.07
TRFER expression Differenti-
ation grade
of BC
−0.39* Negative TRFER/FER ex-
pression correlates with
high differentiation grade
of tumor
FER expression −0.33*
TRFER expression
Metasta-
ses in
regional LN
0.48* Positive TRFER/FER ex-
pression in primary tumor
correlates with develop-
ment of metastases in re-
gional LN
FER expression 0.31*
*Level of significance of correlation coefficient р < 0.05.
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
111ОНКОЛОГИЯ • Т. 16 • № 2 • 2014 111
0,00
20,00
40,00
60,00
80,00
100,00
0,00 10,00 20,00 30,00 40,00 50,00 60,00
TRFER– TRFER+
Pa
tie
nt
s,
%
Time, months
fig. 1. OS of BC patients calculated by Kaplan — Meier me-
thod depending on TRFER expression in TC
0,00
20,00
40,00
60,00
80,00
100,00
0,00 10,00 20,00 30,00 40,00 50,00 60,00
FER– FER+
Pa
tie
nt
s,
%
Time, months
fig. 2. OS of BC patients calculated by Kaplan — Meier me-
thod depending on FER expression in TC
Lack of correlation between level of TRFER and
FER expression in TC of examined patients and stage
and morphological structure of BC, probably, is con-
nected with presence of additional factors of regulation
of stu died proteins on the level of other systems of iron
meta bolism in organism. Data obtained concerning high
level of TRFER and FER expression in tumors of low
diffe rentiation grade is confirmation of participation of
these malignant proteins in proliferation, growth and for-
mation of stage of BC malignancy. This is evidenced by
the results of our previous in vitro studies concerning in-
crease of expression of iron-containing proteins already
in the early stages of malignant transformation of cells of
mammary gland and intensification of evidence of these
di sorders in the process of acquisition by them of more
aggressive mesenchymal phenotype [20, 31].
Determined existence of connections between expres-
sion of studied proteins and development of metastases in
regional LN and survival of BC patients coincides with data
of literature and confirms significance of disorders of iron
metabolism for progression and aggressiveness of clinical
course of BC, as well as confirms fact of cancer ferrotoxici-
ty [32]. For instance, significant expression of TRFER and
FER in TC of BC patients has been determined — 92.2%
of tumors were positive, at that expression of marker di-
rectly correlated with cancer metastases in LN and malig-
nancy of neoplasms [26]. Expression of TRFER (TfR1)
and FER receptors in TC of patients with non-small cell
lung carcinoma was determined in 88 and 62% of tumors
correspondingly [27], but no correlation between indexes
of expression of these markers in cells and their concen-
tration in peripheral blood was determined. Significance
of iron-containing proteins in cancer patients has been
demonstrated also in other studies [18, 19].
Since iron-containing proteins participate in proli-
feration of cells and progression of tumors and are con-
nected with some biological features of tumor growth
and clinical prognosis, they may be considered mole cular
targets for antitumor drugs [9, 33]. Possibility of such
approach to the treatment of cancer patients has been
showed in some experimental studies [34, 35], as well
as is has been confirmed by the results of our previous
studies, which have showed significant increase of ex-
pression of iron-containing proteins in resistant to anti-
tumor drugs cells of BC in vitro and TC of BC patients
resistant to neoadjuvant chemotherapy [21, 22].
Thus, results of carried out study and data of liter-
ature show that iron ions and iron-containing proteins
play important role in metabolism of normal and neo-
plastic cells, can be individual markers of predictive prog-
nosis of survi val of BC patients. Data obtained can be the
basis for deve lopment of new diagnostic criteria and im-
provement of exi sting schemes of antitumor treatment
taking into account indexes of TRFER and FER in TC
of mammary gland.
CONCLUSIONS
1. BC is characterized by intertumor heterogene-
ity of TRFER and FER expression. Part of tumors with
strong positive TRFER and FER expression has consti-
tuted 52.4 і 51.4%, respectively.
2. No correlation between TRFER and FER expres-
sion, on the one hand, and stage of disease and histolo-
gical BC type, on the other hand, has been determined.
3. High differentiation grade of BC correlates
(p < 0.05) with lack of TRFER and FER expression.
4. Positive TRFER and FER expression in cells of pri-
mary tumor of mammary gland correlates with develop-
ment of metastases in regional LN.
5. Prognostic value of TRFER and FER expression
in TC of mammary gland for the evaluation of OS of pa-
tients has been determined. TRFER and FER expression
can be individual predictive marker of survival of BC pa-
tients and one more molecular target for the development
of new antitumor agents.
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ДОСЛІДЖЕННЯ ЕКСПРЕСІї
ТРАНСФЕРИНУ ТА ФЕРИТИНУ
У ПУхЛИННИх КЛІТИНАх хВОРИх
НА РАК МОЛОЧНОї ЗАЛОЗИ
O.В. Шепіль, Н.Ю. Лук’янова, С.В. Чехун,
Л.З. Поліщук, C.В. Антіпова
резюме. Мета: вивчення експресії залізовмісних
білків феритину (ФЕР) і трансферину (ТРФЕР)
у пухлинних клітинах та оцінка її клінічного значен-
ня у хворих на рак молочної залози (РМЗ). Об’єкт
і методи: у дослідження включено 143 пацієнток
із РМЗ ІІ–ІІІ стадії. Методи дослідження: клі-
нічні, морфологічний, імуногістохімічний, статис-
тичний. Результати: показано, що РМЗ характе-
ризується міжпухлинною гетерогенністю експресії
ТРФЕР і ФЕР. Високий ступінь диференціюван-
ня РМЗ корелює з відсутністю експресії ТРФЕР
і ФЕР. Позитивна експресія цих білків у клітинах
первинної пухлини пов’язана з розвитком мета-
стазів у регіонарних лімфатичних вузлах. Вста-
новлено кореляційну залежність між експресією
ТРФЕР та ФЕР у пухлинних клітинах і загальною
виживаністю хворих на РМЗ. Висновки: експресія
ТРФЕР і ФЕР може бути індивідуальним предик-
тивним маркером перебігу хвороби та виживанос-
ті пацієнток із РМЗ і ще однією молекулярною мі-
шенню для розробки нових протипухлинних агентів.
Ключові слова: рак молочної залози,
трансферин, феритин, прогноз.
correspondence:
Lukyanova N.Y.
45 Vasylkivska str., Kyiv 03022
R.E. Kavetsky Institute of Experimental Pathology,
Oncology and Radiobiology of NAS of Ukraine
Received: 25.03.2014
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