الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most common invasive cancer and the leading cause of
cancer death in women. It is the result of dysregulation of gene networks that
maintain normal cellular functions and identity.
Cancerous cells escape from natural proliferation control systems via
different mechanisms which substantially results in genomic changes.
Therefore, these changes can lead to abnormal cell proliferation, unusual cell
movements, unusual cell invasion and even cancerous cell drug resistance.
EMP2 is a member of GAS3/PMP22 group of tetraspan proteins family,
and its expression is upregulated in breast, ovarian and endometrial
malignancies.
The human EMP2 gene mapped to chromosome 16, is well-maintained
across vertebrates. EMP2 functions as a key regulator of cell membrane
composition by regulating protein’s surface expression. Also, it plays a role in
the regulation of processes including cell migration, cell proliferation, cell
contraction, and cell adhesion.
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integrin receptor heterodimers, and the large 12- -Integrin subgroup
bind multiple ECM molecules to activate multiple intracellular pathways and
also induce crosstalk with other signaling systems. The functions of integrin
heterodimers are highly tissue-specific and much human pathology also involve
integrin signaling.
Summary and Conclusion
99
-integrin play a critical role in the maintenance of mammary tissue
integrity. They are essential for the control of cell survival and proliferation
during mammary gland development as well as for mammary epithelial cell
differentiation. -integrin expression has been revealed as necessary for
maintenance of functional mammary stem cells.
This work aimed to study the -integrin
genes in breast cancer tissue.
This study was carried out by cooperation between the Biochemistry
Division, Chemistry Department, Faculty of Science and Medical Biochemistry
and Molecular Biology Department, Faculty of Medicine, Menoufia University.
It included 120 subjects divided into 2 groups.
group I: Included 60 women with breast cancer undergoing modified radical
mastectomy selected from the General Surgery Department, Menoufia
University Hospital, tissue specimens were taken from the cancerous breast
tissues and from the marginal healthy breast tissues.
group II: Included 60 age and sex-matched apparently healthy women served
as a control group.
All studied patients were subjected to full history taking, general clinical
examination, abdominal ultrasound, CT-scan for abdomen, mammography, fine
needle biopsy, histopathological examination, IHC assay, metastatic work up
(chest x-ray and bone scan) and laboratory investigations including: CBC (for
patients and controls), serum CA15-3 (for patients and controls) and detection
the expression of EMP2 and -integrin genes in the breast tissue samples by
formation of cDNA by RT-PCR after RNA extraction and real-time PCR using
SYBR Green technique.
Summary and Conclusion
100
Results
There was a non-significant statistical difference in the age of patients
group as compared with the control group and there was a significant
decrease in RBCs, Hb, HCT and MCHC in patients group as compared
with the control group. While the non-significant decrease in MCH and a
non-significant increase in MCV, WBCs and platelets count in patients
group as compared with the control group. Also there was a significant
increase in CA15-3 in patients group as compared with the control group.
There was a significant increase in both EMP2 -integrin genes
expression in malignant breast tissues as compared with healthy breast
tissues.
There was a significant positive relation between the age and EMP2 gene
expression in healthy breast tissues. While there was a non-significant
positive relation between the age and each of tumor size, grade, stage,
affected lymph node, molecular type, multicentric, carcinoma in situ, ER,
PR, HER2/neu, CA15-3, EMP2 gene expression in malignant breast
-integrin gene expression in healthy and malignant breast
tissues.
There was a significant positive relation between the molecular type and
each of carcinoma in situ, ER, PR, HER2/neu, EMP2 -integrin
genes expression in malignant breast tissues. While a non-significant
positive relation between the molecular type and each of grade, stage,
affected lymph node, multicentric, CA15- -integrin genes
expression in healthy breast tissues.
There was a significant positive relation between the grade and each of
ER and PR in patients and a non-significant positive relation between the
Summary and Conclusion
101
grade and each of stage, affected lymph node, multicentric, carcinoma in
situ, HER2/neu, CA15-3, EMP2 -integrin genes expression in
healthy and malignant breast tissues.
There was a significant positive correlation between grade and the
molecular type and between multicentric and Hb. While there was
a significant negative correlation between grade and WBCs, between
stage and Hb, between stage and WBCs and between carcinoma in situ
and CA15-3.
There was a significant positive correlation between EMP2 and -
integrin in malignant breast tissues and molecular type, while there was a
significant negative correlation between ER and molecular type, between
PR and molecular type, and between EMP2 gene expression in healthy
breast tissues and molecular type.
Univariate analysis of the studied parameters showed that the breast
cancer grade was significantly increased with positive ER, PR, luminal
type and WBCs, while the grade of breast cancer was non-significantly
increased with stage, triple negative type, HER2 positive type,
HER2/neu, Hb and EMP2 expression in malignant breast tissues. Also in
multivariate analysis of the studied parameters the breast cancer grade
was significantly increased with positive luminal type, ER and PR.
Univariate analysis of the studied parameters showed that the EMP2
expression in malignant breast tissues was significantly increased with
positi -integrin expression in malignant
breast tissues, while EMP2 expression in malignant breast tissues was
non-significantly increased with triple-negative type, HER2 positive type,
HER2/neu, -integrin expression in healthy
Summary and Conclusion
102
breast tissues and in multivariate analysis of the studied parameters the
EMP2 expression in malignant breast tissues was non-significantly
increased with positive lumin -integrin expression
in malignant breast tissues.
Univariate analysis of the studied -integrin
expression in malignant breast tissues was significantly increased with
positive age and EMP2 expression in malignant breast tissues.
Furthermore, -integrin expression in malignant breast tissues was
non-significantly increased with carcinoma in situ, HER2 positive type,
HER2/neu, WBCs, platelets and CA15-3. While in multivariate analysis
of -integrin expression in malignant breast
tissues was non-significantly increased with positive age and EMP2
expression in malignant breast tissues.
from the results obtained in this study, we can conclude that
-integrin are important markers for
the severity of breast cancer and they are good indicators of its prognosis.
When the gene expression of the EMP2 elevated in breast cancer tissue it
is usually accompa -integrin and CA15-3.