Breast cancer immunohistochemical features in young women with BRCA1/2 mutations
Breast cancer among young women is a rare pathology. In most studies published so far, this patients group is not being analyzed separately. Particularities of this pathology require an additional examination of the immunohistochemical and molecular-genetic markers of the disease for development of...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2009
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| Цитувати: | Breast cancer immunohistochemical features in young women with BRCA1/2 mutations / L.M. Zakhartseva, N.G. Gorovenko, S.V. Podolskaya, N.F. Anikusko, O.E. Lobanova, K.A. Pekur, V.A. Kropelnytskyi, O.V. Shurygina // Experimental Oncology. — 2009. — Т. 31, № 3. — С. 174-178. — Бібліогр.: 28 назв. — англ. |
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nasplib_isofts_kiev_ua-123456789-1344042025-02-09T13:44:50Z Breast cancer immunohistochemical features in young women with BRCA1/2 mutations Zakhartseva, L.M. Gorovenko, N.G. Podolskaya, S.V. Anikusko, N.F. Lobanova, O.E. Pekur, K.A. Kropelnytskyi, V.A. Shurygina, O.V. Original contributions Breast cancer among young women is a rare pathology. In most studies published so far, this patients group is not being analyzed separately. Particularities of this pathology require an additional examination of the immunohistochemical and molecular-genetic markers of the disease for development of the effective treatment protocols. The mutations of BRCA1/2 are the important factor impacting to the disease prognosis along the age of the patient. Aim: To compare the expression of prognostically meaningful immunohistochemical markers such as estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Ki-67, in tumor cells of the female patients with breast cancer aged less than 36 depending on the presence or absence of mutations in BRCA1/2 genes. Methods: Two hundred forty-eight patients aged less than 36 at the time of diagnosis of breast cancer were examined clinically. Expression of ER, PR, HER-2, p53, Ki-67 was determined by indirect immunohistochemical method. Mutations of BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) genes were screened using multiplex PCR in 99 patients. Results: Mutations of BRCA1/2 genes were found in 9.1% of patients. More aggressive clinical course of the disease was seen in mutations carriers, who had 3-years survival of only 55.6%. They did not demonstrated expression of ER, PR, and HER-2 in 88.9% of the cases. Whereas, patients without BRCA1/2 mutations did not express ER, PR, and HER-2 in only 42.0% of cases. There were no diffe rences between patients with and without mutations in terms of tumor size, presence of metastases in lymph nodes, p53 and Ki-67 expression. Conclusion: Presence of BRCA1/2 genes mutations in young women is associated with more aggressiveness of the breast cancer (their 3-years survival is 25, 5% less) and absence of the ER, PR, HER-2 receptors, which is unfavorable prognostic factor in terms of hormone therapy. These data should be taken into account at chemotherapy planning, especially in patients with early stages of the disease. There were no differences between patients with and without BRCA1/2mutations in terms of tumor size, lymph nodes involvement, tumor histology, and p53 and Ki-67 proteins expression. 2009 Article Breast cancer immunohistochemical features in young women with BRCA1/2 mutations / L.M. Zakhartseva, N.G. Gorovenko, S.V. Podolskaya, N.F. Anikusko, O.E. Lobanova, K.A. Pekur, V.A. Kropelnytskyi, O.V. Shurygina // Experimental Oncology. — 2009. — Т. 31, № 3. — С. 174-178. — Бібліогр.: 28 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/134404 en Experimental Oncology 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 |
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DSpace DC |
| language |
English |
| topic |
Original contributions Original contributions |
| spellingShingle |
Original contributions Original contributions Zakhartseva, L.M. Gorovenko, N.G. Podolskaya, S.V. Anikusko, N.F. Lobanova, O.E. Pekur, K.A. Kropelnytskyi, V.A. Shurygina, O.V. Breast cancer immunohistochemical features in young women with BRCA1/2 mutations Experimental Oncology |
| description |
Breast cancer among young women is a rare pathology. In most studies published so far, this patients group is not being analyzed separately. Particularities of this pathology require an additional examination of the immunohistochemical and molecular-genetic markers of the disease for development of the effective treatment protocols. The mutations of BRCA1/2 are the important factor impacting to the disease prognosis along the age of the patient. Aim: To compare the expression of prognostically meaningful immunohistochemical markers such as estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Ki-67, in tumor cells of the female patients with breast cancer aged less than 36 depending on the presence or absence of mutations in BRCA1/2 genes. Methods: Two hundred forty-eight patients aged less than 36 at the time of diagnosis of breast cancer were examined clinically. Expression of ER, PR, HER-2, p53, Ki-67 was determined by indirect immunohistochemical method. Mutations of BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) genes were screened using multiplex PCR in 99 patients. Results: Mutations of BRCA1/2 genes were found in 9.1% of patients. More aggressive clinical course of the disease was seen in mutations carriers, who had 3-years survival of only 55.6%. They did not demonstrated expression of ER, PR, and HER-2 in 88.9% of the cases. Whereas, patients without BRCA1/2 mutations did not express ER, PR, and HER-2 in only 42.0% of cases. There were no diffe rences between patients with and without mutations in terms of tumor size, presence of metastases in lymph nodes, p53 and Ki-67 expression. Conclusion: Presence of BRCA1/2 genes mutations in young women is associated with more aggressiveness of the breast cancer (their 3-years survival is 25, 5% less) and absence of the ER, PR, HER-2 receptors, which is unfavorable prognostic factor in terms of hormone therapy. These data should be taken into account at chemotherapy planning, especially in patients with early stages of the disease. There were no differences between patients with and without BRCA1/2mutations in terms of tumor size, lymph nodes involvement, tumor histology, and p53 and Ki-67 proteins expression. |
| format |
Article |
| author |
Zakhartseva, L.M. Gorovenko, N.G. Podolskaya, S.V. Anikusko, N.F. Lobanova, O.E. Pekur, K.A. Kropelnytskyi, V.A. Shurygina, O.V. |
| author_facet |
Zakhartseva, L.M. Gorovenko, N.G. Podolskaya, S.V. Anikusko, N.F. Lobanova, O.E. Pekur, K.A. Kropelnytskyi, V.A. Shurygina, O.V. |
| author_sort |
Zakhartseva, L.M. |
| title |
Breast cancer immunohistochemical features in young women with BRCA1/2 mutations |
| title_short |
Breast cancer immunohistochemical features in young women with BRCA1/2 mutations |
| title_full |
Breast cancer immunohistochemical features in young women with BRCA1/2 mutations |
| title_fullStr |
Breast cancer immunohistochemical features in young women with BRCA1/2 mutations |
| title_full_unstemmed |
Breast cancer immunohistochemical features in young women with BRCA1/2 mutations |
| title_sort |
breast cancer immunohistochemical features in young women with brca1/2 mutations |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2009 |
| topic_facet |
Original contributions |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/134404 |
| citation_txt |
Breast cancer immunohistochemical features in young women with BRCA1/2 mutations / L.M. Zakhartseva, N.G. Gorovenko, S.V. Podolskaya, N.F. Anikusko, O.E. Lobanova, K.A. Pekur, V.A. Kropelnytskyi, O.V. Shurygina // Experimental Oncology. — 2009. — Т. 31, № 3. — С. 174-178. — Бібліогр.: 28 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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| first_indexed |
2025-11-26T10:01:48Z |
| last_indexed |
2025-11-26T10:01:48Z |
| _version_ |
1849846725927239680 |
| fulltext |
174 Experimental Oncology 31, 174–178, 2009 (September)
Breast cancer is one of the most common malignant
tumors and a main cause of death from oncological
diseases in women worldwide. One third, and in eco-
nomically developed countries up to 40% of all cases
of breast cancer is diagnosed in female patients older
than 65 years [1]. Young patients account from 2 to 5%
of all breast cancer population [2–4]. In Ukraine the
incidence of women for breast cancer increases with
the age of the patients, reaching maximum in age
group of 70–74 (148.9 per 100 000 of female popula-
tion), then decreases in age groups of 75–79, 80–84,
85 years and older where accounts 113.2, 108.5 and
74.3 per 100 000 of female population respectively.
The rate of morbidity for breast cancer in age groups
of 15–19 years, 20–24 years, 25–29 years, 30–
34 years is 0.1, 1.3, 3.2 and 13.7 per 100 000 of female
population accordingly [3]. As this pathology is rare
in young women, there are limited studies published
so far on early breast cancer. Most of them are based
on the data obtained from the retrospective studies
on the small number of cases [2, 4].
The early breast cancer is often characterized by the
presence of a low histological differentiation, high mi-
totic activity, and frequent vascular wall invasion. There
is no common opinion regarding the age peculiarities
of Her2/neu, р53, progesterone receptor expression
[5–8]. There are controversial data on tumor sizes and
lymph nodes involvement characteristics in patients
with early breast cancer. M. Colleoni et al. [9] did not
observe the bigger size of tumor and lymph nodes
involvement in young female patient in contrast to the
opinion of a numerous authors who reported it [7, 10].
W. Lee et al. [11] demonstrated the absence of diffe-
rences in Her2/neu and p53 expression in cells of breast
cancer female patients in young and elderly age.
Many investigators pointed out the shorter three- and
five-years survival of young female patients in comparison
with elderly females in premenopausal and postmeno-
pausal age. This was the reason to include the age into
the list of negative prognostic factors in breast cancer.
Young female patients (35 years old and younger) need
more chemotherapy compared to the older patients ac-
cording to recommendations of St Gallen consensus.
There are a lot of studies demonstrated that cancer
patient’s survival depends not only on the stage of the
disease, but also on the intrinsic biological factors,
which predispose the characteristics of the tumors.
The key neoplastic event is the genetic change, which
leads to uncontrolled cell growth, loss of ability to dif-
ferentiate and disturbance of apoptosis. Situation with
the molecular-genetic features of the early breast
cancer is not clear. The changes in estrogen recep-
tor (ER), progesterone receptor (PR), HER-2/neu
BREAST CANCER IMMUNOHISTOCHEMICAL FEATURES IN YOUNG
WOMEN WITH BRCA1/2 MUTATIONS
L.M. Zakhartseva1, *, N.G. Gorovenko2, S.V. Podolskaya2, N.F. Anikusko1,
O.E. Lobanova3, K.A. Pekur1, V.A. Kropelnytskyi1, O.V. Shurygina1
1Kyiv City Oncological Hospital, Kiev 03115, Ukraine
2P.L. Shupyk National Medical Academy of Postgraduate Education, Kiev 04112, Ukraine
3A.A. Bohomolets National Medical University, Kiev 01601, Ukraine
Breast cancer among young women is a rare pathology. In most studies published so far, this patients group is not being analyzed
separately. Particularities of this pathology require an additional examination of the immunohistochemical and molecular-genetic
markers of the disease for development of the effective treatment protocols. The mutations of BRCA1/2 are the important factor
impacting to the disease prognosis along the age of the patient. Aim: To compare the expression of prognostically meaningful im-
munohistochemical markers such as estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Ki-67, in tumor cells of the
female patients with breast cancer aged less than 36 depending on the presence or absence of mutations in BRCA1/2 genes. Methods:
Two hundred forty-eight patients aged less than 36 at the time of diagnosis of breast cancer were examined clinically. Expression
of ER, PR, HER-2, p53, Ki-67 was determined by indirect immunohistochemical method. Mutations of BRCA1 (185delAG,
5382insC) and BRCA2 (6174delT) genes were screened using multiplex PCR in 99 patients. Results: Mutations of BRCA1/2 genes
were found in 9.1% of patients. More aggressive clinical course of the disease was seen in mutations carriers, who had 3-years
survival of only 55.6%. They did not demonstrated expression of ER, PR, and HER-2 in 88.9% of the cases. Whereas, patients
without BRCA1/2 mutations did not express ER, PR, and HER-2 in only 42.0% of cases. There were no diffe rences between patients
with and without mutations in terms of tumor size, presence of metastases in lymph nodes, p53 and Ki-67 expression. Conclusion:
Presence of BRCA1/2 genes mutations in young women is associated with more aggressiveness of the breast cancer (their 3-years
survival is 25, 5% less) and absence of the ER, PR, HER-2 receptors, which is unfavorable prognostic factor in terms of hormone
therapy. These data should be taken into account at chemotherapy planning, especially in patients with early stages of the disease.
There were no differences between patients with and without BRCA1/2 mutations in terms of tumor size, lymph nodes involvement,
tumor histology, and p53 and Ki-67 proteins expression.
Key Words: breast cancer, young patients, BRCA1/2 gene mutations, immunohistochemical markers.
Received: August 26, 2009.
*Correspondence: Fax: +38 (044) 444-68-18
E-mail: lmz@list.ru
Abbreviations used: ER — estrogene receptor; PCR — polymerase
chain reaction; PR — progesterone receptor.
Exp Oncol 2009
31, 3, 174–178
Experimental Oncology 31, 174–178, 2009 (September) 175
expression, presence of apoptotic markers, changes
of indices of proliferative activity are demonstrated
for breast cancer patients of young age [12]. How-
ever, in spite these characteristics have the clinical
prognostic value, the protocols of early breast cancer
diagnostics and treatment urgently need an improve-
ment. A lot of young breast cancer patients received
too aggressive therapy, whereas, some of them are
not effectively treated and died prematurely. It is very
important to have the objective molecular-biologic
criteria, which could classify the aggressiveness
of cancer in young patients. The BRCA1/2 mutations
are very common in young breast cancer patients.
Thus, it could be assumed that they play an important
role in carcinogenesis and predetermine the prognosis
[13]. There are numerous studies linked BRCA1/2 mu-
tations with unfavorable clinical prognosis [14, 15].
BRCA1 (ОМIM 113705) and BRCA 2 (OMIM 600185)
genes are associated with the prevalence of hereditary
forms of breast cancer and ovary cancer. The presence
of germinal mutations of BRCA1 and BRCA2 genes
increases the risk of the disease in women aged
50 by 30–50% and in women of 80 years old by 60–
90% [16–18]. The spectrum and frequency of muta-
tions in BRCA1 and BRCA2 genes differs in various
ethnic groups, therefore, special investigations are
needed for each population [19–25].
Pathogenesis of BRCA-associated and sporadic
breast cancer have a lot of differences. It has been
demonstrated that the size of the breast tumor in car-
riers of BRCA1/2 mutations is greater and the absence
of regional lymph nodes involvement does not lead
to the decrease of mortality in carriers of mutated genes.
Tumors associated with pathologic BRCA-genotype
have a short duplication period, higher malignancy
level. According to the majority authorsʼ data, 64–92%
of tumor cases associated with germinal mutations
of BRCA1/2 genes do not have receptors of estrogen
and progesterone; although in some cases patients with
BRCA2 mutations have paradoxically high expression
of receptors of steroid hormones. One might consider
germinal mutations of BRCA genes as molecular-genetic
markers that have a prognostic value. The development
of diagnostic algorithm needs receiving sufficient data
for selecting the most effective treatment regimen
for young breast cancer female patients. Immunohis-
tochemical and genetic investigations methods acquire
a particular value currently. The most authors report that
patients with BRCA1/2 mutations have bigger tumor
size, more often have metastasis in lymph nodes and
rarely express ER and PR [26]. The data on Her-2, р53,
Кі-67 in BRCA1/2 carriers are controversial.
MATERIALS AND METHODS
The investigation was carried out on 248 retrospec-
tive and prospective cases of breast cancer in women
younger 36 years of age who had been treated at the
Kiev City Oncological Hospital through 1997–2007,
which accounted 3.2% of all hospital patients suffer-
ing from this pathology. All patients provided written
consent to perform the study.
In majority of cases, tumor size was small: Т1 —
142 cases (57.3%), Т2 — 85 cases (34.3%), Т3 —
16 cases (6.5%), and Т4 — 5 cases (2.0%). Initial disease
stages were seen more often: I stage (Т1-2N0M0) —
46.8%, II stage (Т1-2N0-1M0) — 43.2%. In 127 cases
patients underwent mastectomy (51.21%), in 83 cas-
es — tissue-sparing operation (33.5%), and 38 patients
underwent only conservative treatment (15.3%). Verifica-
tion of the diagnosis was done by histology on the core
biopsy material. In the majority of cases, tumor was dia-
gnosed as an infiltrating ductal carcinoma — 233 cases
(93.95%), in some cases — infiltrating lobular carcinoma
(8 cases), medullar (3 cases), giant cellular (1 case),
squamous cell (1 case) carcinoma, carcinosarcoma
(1 case), Pedget cancer (1 case).
Paraffin-embedded tumor sections from 99 pa-
tients were used for immunohistochemical investi-
gation. Indirect immunohistochemical methods with
monoclonal antibodies against estrogen (clone 1D5),
progesterone (clone PgR 636), oncoprotein c-erbB-2
(HER-2/neu), p53, Ki-67 and LSAB and EnVision vi-
sualization system (DAKO) were used. Results were
assessed by calculating the percentage of tumor cells,
having stained nucleus with indication of intensivity
of staining (from 1+ to 3+). In assessing the results
of reaction with c-erbB-2 antibody we registered the
presence of intensive membrane staining of the cell
(from 1+ to 3+). Tumors with detected staining inten-
sivity 2+ and 3+ were considered to be positive.
In 99 from 248 young patients the mutations
in BRCA1/2 genes (mutations 5382ins and 185delAG
in BRCA1 gene, and mutation 6174delТ in BRCA2 gene)
were screened using DNA isolated from peripheral blood
or from formalin fixed paraffin-embedded tumor tissue
sections if the patient was dead at the time of cases
recruitment. DNA isolation from paraffin-embedded
sections was performed using method suggested
by J.L. Bernstein et al. [27]. DNA isolation from peripheral
blood was performed by a standard method using a com-
mercial test-system DNA Sorb B kit (AmpliSens).
The conditions of DNA amplification and primers
sequence for detecting of mutations 5382ins and
185delAG in BRCA1 gene, 6174delT in BRCA2 gene
were published earlier by P.C. Chan et al. [28].
RESULTS AND DISCUSSION
Mutations of BRCA1/2 have been detected in 9 fe-
male patients from cohort of 99 breast cancer young
patients (9.1%). Mutation 185delAG in BRCA1 gene was
detected in 1 patient, mutation 5382ins in BRCA1 gene —
in 7 patients, mutation 6174delT in BRCA2 gene —
in 1 patient (Table 1). During the first year after making
the diagnosis, 4 patients from 9 died (44.4%). The other
5 young women lived over 3 years, and 3 of them lived
over 5 years after surgical intervention. Thus, 3-years
survival reached 55.6%. In the group of living patients,
T1N0M0 was diagnosed in 3 cased, and T2N1M0 —
in one case. The size of tumor corresponding to Т1 had
176 Experimental Oncology 31, 174–178, 2009 (September)
44.4% patients with mutations of BRCA1/2 genes,
Т2 — 34%, Т3 — 21.5%. Lymph nodes metastases were
detected in 33.3% of patients. One of the died patient
of this group had the I stage of disease (T1N0M0), the
second one — II stage without lymph nodes involvement
(T2N0M0) and only 2 patients had metastases in lymph
nodes (T2N1M0 и T3N1M0). Thus, probably, aggressive
course of the disease in those women is not predeter-
mined by the advanced stage of the disease at the mo-
ment of diagnosis but rather by biology of tumor.
Table 1. The results of immunohistochemical studies of young women
with breast cancer and BRCA1/2 mutations
Ca
se
TN
M
Ty
pe
G
ra
de Immunohistochemical staining Survival
rateER PR Her-2/
neu
Ki-
67 p53
Mutation 5382 insC in BRCA1gene
1 T1N0M0 Ductal
carcinoma
I Neg Neg Neg 90% 60% Alive
6 years
2 T2N1M0 Lobular
carcinoma
II Neg Neg Neg 23% 20% Alive
10 years
3 T1N0M0 Ductal
carcinoma
II Neg Neg Neg 70% 70% Alive
3 years
4 T1N0M0 Ductal
carcinoma
I Pos Pos Neg 40% 20% Alive
5 years
5 T1N0M0 Ductal
carcinoma
II Neg Neg Neg 68% 70% Lived less
than 1 year
6 T2N0M0 Ductal
carcinoma
II Neg Neg Pos 53% 100% Alive
4 years
7 T3N1M0 Ductal
carcinoma
II Neg Neg Pos 75% 100% Lived less
than 1 year
Mutation 185 del AG in BRCA1 gene
8 T2N1M0 Ductal
carcinoma
III Neg Neg Neg 60% 100% Lived less
than 1 year
Mutation 6174 del T in BRCA2 gene
9 T3N0M0 Ductal
carcinoma
III Neg Neg Pos 40% 90% Lived less
than 1 year
Notes: In Tables 1, 2, 3: Neg — negative; Pos — positive.
In the group of young age patients without mutations
in BRCA1/2 genes small size of tumors was predominant:
Т1 in 46.6% of cases, Т2 — in 44.4%, Т3 — in 8.8%, Т4 —
in 0.2%. More than half of the patients (51.6%) did not
have metastases in lymph nodes and 46% of patients had
metastases lesions in only one group of lymph nodes,
2.4% — in two groups. 81.1% of female patients lived
3 and more years. No differences in histological cancer
variants in women with mutations of BRCA1/2 and with-
out mutations were found.
Therefore, in cases of similar disease stages
and similar histological cancer types, the clinical
course of breast cancer in young age patients ha-
ving BRCA1/2 genes mutations was more aggres-
sive. The index of 3-years survival of patients with
BRCA1/2 genes mutations was lower by 25.6%.
Estrogen and progesterone receptors expression was
seen only in one case out of 9 (11.1%) patients with muta-
tions in BRCA1/2 genes (Fig. 1, 2), whereas in patients
without mutations 57.97% of the cases have an estrogen
receptor (p < 0.05) and 56.52% of the cases have a pro-
gesterone receptor (p < 0.05) (Table 2, 3).
Table 2. ER and PR status in women with and without BRCA1/2 mutations
(mean)
Young women < 36 years
With BRCA1/2
mutations
Without BRCA1/2
mutations All young women
ER Pos 11.11% 57.97% 49.3%
PR Pos 11.11% 56.52% 47.3%
Neg 88.89% 43.48% 52.7%
Table 3. Estrogen (ER) and progesterone receptor (PgR) status in women
with and without BRCA1/2 mutations
Immunohis-
tochemical
staining
Results
Young women < 36 years
With BRCA1/2
mutations, %
Without BRCA1/2
mutations, %
All young
women, %
ER Pos 8.3 ± 7.9 41.4 ± 4.7 38.2 ± 4.4
PR Pos 8.3 ± 7.9 44.1 ±4 .7 40.6 ± 4.4
HER-2 Pos 16.7 ± 10.8 6.3 ± 2.3 7.3 ± 2.3
p 53 > 40% 58.3 ± 14.2 15.3 ± 3.4 19.5 ± 3.6
Ki-67 > 40% 50 ± 14.4 16.2 ± 3.5 19.5 ± 3.6
a
b
Fig. 1. Estrogen receptor expression by breast tumor cells. a, Estrogen
receptor has a nuclear expression in the majority of the tumor cells.
b, Case with negative estrogen receptor expression. Immunohistoche-
mistry staining, visualisation system EnVision, chromogene DAB, X 400
Fig. 2. Progesteron receptor has a nuclear expression in the
majority of the tumor cells. Immunohistochemistry staining,
visualisation system EnVision, chromogene DAB, X 400
Overexpression of oncoprotein HER2/neu was
observed in 3 cases from 9 in patients with mutation
of BRCA1/2 genes (33.3%) and in 13.85% in breast can-
Experimental Oncology 31, 174–178, 2009 (September) 177
cer women without mutations of those genes (Fig. 3).
Protein p53 expression in more than 50% of tumors cells
was observed in 6 cases from 9 in case of the presence
of BRCA1/2 genes mutation (66.7%) and in 50% of fe-
male patients without mutations of those genes (Fig. 4).
Mitotic tumor activity in patients of the both groups was
insignificantly different: high mitotic index 57.1% was
in mutated breast cancer women and in 50% cases
in unmutated breast cancer patients (Fig. 5).
Fig. 3. HER-2/neu (C-erB-2 oncoprotein) (2+) membrane
expression in the tumor cells. Immunohistochemistry staining,
visualisation system EnVision, chromogene DAB, X 400
Fig. 4. P53 protein was expressed by all tumor cells. Immunohistoche-
mistry staining, visualisation system EnVision, chromogene DAB, X 400
Fig. 5. Ki-67 protein was expressed in 70% of the tumor cells.
Immunohistochemistry staining, visualisation system EnVision,
chromogene DAB, X 400
In conclusion, BRCA1/2 genes mutations were
found in 9.1% of the patients. No differences in histo-
logical cancer variants and disease stages in women
with mutations of BRCA1/2 and without mutations were
found. The presence of mutations in BRCA1/2 genes
in young women is associated with more aggressive
course of the breast cancer and absence of the pro-
gesterone and estrogene receptors (see Fig. 1), which
is unfavorable prognostic factor.
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