الفهرس 
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Abstract
Cancer is a major health problem world wide and the
morbidity and mortality from cancer give rise to much suffering.
Breast cancer is the most common malignancy in women
worldwide. The adhesion proteins are involved in many of the
intermediate steps of metastasis cascade and are likely to show
pronounced changes in expression during malignant progression.
Four major classes of adhesion molecules have been described.
The first class of adhesion molecules is the
immunoglobulin-like superfamily consisting of membrane proteins
that are organized into pleated sheets. They include Intracellular
adhesion molecules-1 (ICAM-1) and Vascular cell adhesion
molecule-1 (VCAM-1). The activity and expression of these
molecules are upregulated following inflammation. Interactions
between integrins and intracellular adhesion molecules result in
strong bonds, which facilitate adhesion and subsequent diapedesis
of leukocytes. ICAM-1 is involved in leukocyte adhesion and
VCAM-1 is involved in adhesion and diapedesis.
The second class of adhesion molecules is selectins which
involved in early phase of the adhesion cascade. They allow
between endothelial cells and leukocytes, resulting in the
phenomenon of leukocyte rolling.
They are subdivided into 3 subgroups, E, P and L, denoting
their association with endothelial cells, platelets and leukocytes,
Summary and Conclusions
1 38
respectively. E-selectin is expressed at low concentrations on
endothelial cells and is synthesized de novo and rapidly upregulated
following stimulation by inflammatory mediators. The third classes
of adhesion molecules are the integrins, which are transmembrane
proteins composed of 2 subunits, α and β. The fourth class are the
cadherins, which are mediators of cell-cell interactions. These are
calcium-dependent transmembrane glycoproteins that form
homophilic interactions. Adhesion molecules are important in cellcell
and cell-basement membrane interactions. They are intimately
involved in inflammatory reactions and a role in tumor progression
has been postulated. E-selectin, ICAM-1 and VCAM-1 play a role
in cell adhesion to the vascular endothelium, which precedes
extravasation of cells and development of metastases. This study
included 50 patients with primary breast cancer in different stages,
in addition to 17 Patient’s with a benign breast tumour
(Fibroadenoma) and 21 normal healthy women. Serum levels of
soluble VCAM-1 and soluble E-selectin were measured with
commercial sandwich ELISA assays and compared with
clinicopathological information.
· Pre-operative serum mean levels of soluble E-selection and
VCAM-1 were significantly increased compared with the
mean levels in breast cancer group and control group
(P < 0.0001).
Summary and Conclusions
1 39
· Slightly elevated mean level of soluble VCAM-1 in benign
group compared to control group but statistically
insignificant (P = 0.114).
· Slightly elevated mean level of soluble E-selectin in benign
group comparable to control group but statistically
insignificant (P = 0.337).
· Very highly significant elevated soluble VCAM-1 and
soluble E-selectin in both positive and negative lymph node
groups comparable with benign and control groups
(P < 0.0001).
· In comparison between positive and negative lymph node
groups there was a very highly significant elevated mean
level of soluble VCAM-1 and soluble E-selectin in lymph
node positive (P < 0.0001).
· A highly significant elevated mean level of soluble ESelectin
in stage I group comparable to benign group
(P = 0.0005) .
· Slightly elevated levels of soluble E-Selectin in stage II
group comparable to stage I group but statistically
insignificant between both studied groups (P = 0.127).
· Avery highly significant elevated mean level of soluble
VCAM-1 in stage I group comparable to benign group
(P < 0.0001).
Summary and Conclusions
1 40
· Very highly significantly elevated mean level of soluble
VCAM-1 in stage II group in comparison with stage I
group (P < 0.0001).
· Very highly significant elevated mean level of soluble Eselectin
and soluble VCAM-1 in stage III group compared
to stage I and stage II groups (P < 0.0001).
CONCLUSIONS
This study involved only 50 subjects, we can conclude that
there is an association between shedding of soluble E-selectin and
VCAM-1 and established prognostic factors in breast cancer.
· For biomarker to be useful as monitor of a pathological
process , it must be easily measurable , must be reflect
accurately the pathological process that it is designed to
measure, and must provide the clinician with an answer that
can easily interpreted. Serum E-selsctin and VCAM-1
fulfills these criteria as a clinical measure of tumor growth
and metastasis.
· Soluble VCAM-1 is an accurate marker of tumor
angiogenesis in breast cancer.
Summary and Conclusions
1 41
· Soluble E-selectin can be used as tumor marker that is
closely correlated with the metastatic status in breast cancer
(soluble E-selectin reflects the severity of invasive breast
cancer).
· Levels of several epithelial tumor markers may rise intialy
in responding tumors in the so-called ( flare response) but
the major source of VCAM-1 and E-selectin in tumors is
endothelial cells not epithelial cells, so serum VCAM-1 and
E-selectine may prove to be an early and sensitive marker
for breast cancer.
· The combination of an endothelial markers and epithelial
marker may be better than multiple epithelial tumor marker
measures in predicting breast cancer.
· Further studies on a large sample size are needed to evaluate
VCAM-1 and E-selectin as a possible target for
antimetastatic therapy through modulation of expression of
this cell adhesion molecule. Anti E-selectin and Anti
VCAM-1 approaches could be a promising strategy for
improving tumor therapy.