الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most common cancer worldwide among women
both in developed and developing countries. More than a million women
are diagnosed every year. In Egypt; National cancer Institute (NCI) stated
that, breast cancer came as number one in ranking of malignant tumors
constituting 17.50% of total malignancies, and breast cancer constitutes
33% of all female cancers.
There were several prognostic factors that can be used to categorize
breast carcinoma into those with a good or poor prognosis and so could
influence the management of breast carcinoma. They include lymph node
status, tumor size, distant metastasis, histological grade, ER and PR
hormonal receptors, HER2/neu overexpression, age and lympho-vascular
invasion.
Breast cancer stem cells - the first to be identified in a solid tumor -
were discovered in 2003. It was found that just a few cancer stem cells
are responsible for the growth and spread of breast cancer. So it is
important to know in the first what is stem cells and so cancer stem cells.
It was found that every organ and type of tissue in the body contains
a small number of ”adult” or ”tissue” stem cells. As most cells in the body
live for just a short time, there is need to keep making new cells to
replace them. Adult stem cells ensure a continuous supply of new cells to
replace old cells that wear out or destroyed.Stem cells have properties
that make them different from the ordinary cells; as they divide,
differentiate and duplicate.
Cancer stem cells were found within tumors that possess
characteristics associated with normal stem cells. Therefore CSCs are
Summary
124
tumorigenic, through the stem cell processes of self-renewal and
differentiation into multiple cell types.
All stem cells have a unique pattern of proteins, like a fingerprint, on
their surface membranes. Breast cancer stem cells have a surface protein
marker called CD44as well as a cytoplasmic protein called ALDH, which
are produced by cancer stem cells and can be detected in biopsies of
patient’s tumors.
CD44 participates in a wide variety of cellular functions including
lymphocyte activation, recirculation and homing, hematopoiesis, cell–cell
interactions, cell adhesion and migration. As an important adhesion
molecule, CD44 plays a major role in cancer cell migration and tumor
metastasis.
ALDH1 is involved in the cellular differentiation and proliferation.
Therefore, ALDH may have a role in early differentiation of stem cells.
The breast carcinoma cells with ALDH1 participate in the acquisition of
progenitor features and it plays important functional roles related to selfprotection.
The word morphometry is defined as “the quantitative description of
the structure. The reasons for increasing interest for application of
morphometry in diagnostic pathology are its advantage of objectivity,
reproducibility and possibility of detecting minor differences or variations
in a specimen that would otherwise escape subjective evaluation.
The usage of quantitative methods in combination with other objective
prognostic criteria can improve the evaluation of the patient’s prognosis,
and possibly predict response to therapy. So the nuclear morphometry
could be one of the important prognostic and predictive markers.
Summary
125
The aim of this work was to detect the cancer stem cells in invasive
duct breast carcinoma by using CD44 and ALDH1 markers, to correlate
CD44 and ALDH1 expression with prognostic factors of duct breast
carcinoma (age, tumor size, tumor histological grade, tumor stage,
hormonal receptors), to analyze breast ductal cancer cells
morphometrically and to compare CD44 and ALDH1 expression with the
morphometric parameters.
The material of this study consisted offive control samples of normal
breast tissue and eighty of formalin fixed retrospectiveparaffin-embedded
tissue samples with breast cancer diagnosed as invasive duct carcinoma
NOS. All cases were subjected to the H&E stain for histopathological
examination to confirm diagnosis, to asset histological grading of tumors
and morphometrical analysis. Also, IHC staining was done to evaluate
expression of stem cell markersCD44 and ALDH1 expression with
prognostic factors of breast carcinoma (ER, PR, Her2/neu).
Out of studied 80 cases,sixty nine cases were CD44 positive
(twenty one were +1, twenty four were +2 and twenty four were +3).
Twenty nine cases were ALDH1 positive. Sixty six cases were ER
positive (ten were weak, eleven were moderate and forty five were
strong). Fifty five cases were PR positive (eleven were weak, twelve were
moderate and thirty two were strong). Twelve cases were Her2/neu
positive (+3 &+2 FISH +ve). Concerning morphometrical analysis the
minimum mean area measured was 54.43 μm2and the maximum mean
area measured was139.16 μm2.The minimum mean nuclear size
calculated was 4.117 μm2and the maximum mean nuclear size calculated
was 6.656 μm2.
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126
Statistically, in the current study there was a significant direct
correlation between CD44 expression and tumor grade as well as tumor
stage. While, there was a significant inverse correlation between CD44
expression and ER hormonal state.
There was a statistically significant direct correlation in the present
study between ALDH1 expression and tumor grade. But, there was a
statistically significant inverse correlation between ALDH1 expression
and ER hormonal state.
This work showed a statistically significant direct correlation
between the mean nuclear size and tumor grade, tumor stage as well as
andCD44 and ALDH1 immunostain expression. However, there was a
significant inverse correlation between mean nuclear size with ER
hormonal state.
No correlation could be detected in the present study between both
of CD44& ALDH1 immunohistochemichal results and each of age, tumor
size, PR hormonal state and Her2/neu.
In this study also there is no correlation could be detected between
nuclear morphometrical parameters and PR hormonal state, Her2/neu as
well as tumor size.