الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Urinary bladder cancer shows a steady worldwide increase in incidence and it accounts
for the 11th most common worldwide and the 3rd most common in Egypt, making it one of the
most common cancers in Egypt.
Generally, urinary bladder cancer is more prevalent among males rather than females. The
most common histological type is Urothelial carcinoma representing 90% of cases. There are
two types of bladder cancer: non-muscle invasive bladder cancer (NMIBC) and Muscle
invasive bladder cancer (MIBC).
Treatment options are limited and unchanged and represented in TURBT followed by
intravesical chemo- or immunotherapy or radical cystectomy followed by systemic
chemotherapy. Therefore, there is a growing need to investigate molecular pathways of urinary
bladder cancer development and to explore new treatment options.
Androgen receptor is a steroid sex hormone receptor normally expressed in urethral and
urinary bladder epithelium. AR is a cytoplasmic receptor that when bound to androgen
translocates into the nucleus and causing transcription of several genes. Its role is widely not
understood however according to many studies AR signalling has been reported to contribute to
urinary bladder oncogenesis, progression, chemo- and radioresistance.
Human Epidermal Growth Factor Receptor-2 (HER2) is a type I tyrosine kinase
transmembrane growth factor receptor involved in cycle cell regulation and cell proliferation.
HER2 gene amplification and subsequent protein overexpression are associated with
oncogenesis and malignant transformation.
The aim of this work is to study the expression of Androgen Receptor and HER2 in
Urothelial carcinoma with various degrees of invasion and its correlation with patient’s age,
gender, grade of the tumor, presence of vascular invasion and recurrence.
The present work was conducted on 50 cases of urothelial carcinoma of the urinary
bladder of TURBT specimens collected retrospectively between 2019 and 2021 from the
archive of the Pathology department, Medical Research Institute, Alexandria university and
other private labs.
All specimens were examined by routine Hematoxilyn and Eosin staining for diagnosis.
Immunohistochemical staining was performed on the studied cases for AR and HER2 and was
considered positive in the presence of any intensity of nuclear staining for AR and of the
membrane for HER2. The current work assessed correlation between clinicopathological
parameters of the studied cases and immunohistochemical expression of AR and HER2.
The studied cases included 38 cases of NMI urothelial carcinoma including 22 (Stage Ta)
and 16 (Stage T1). The MI urothelial carcinoma group (stage T2) included 12 cases. In the stage
Ta group 20 cases were low grade and 2 cases were high grade, the stage T1 group included 9
low grade cases and 7 high grade cases and all 12 cases in the stage T2 group were high grade.
In the current study there was a statistically significant correlation between AR expression
and higher stage (P<0.001), higher grade (P= 0.003) and presence of lymphovascular invasion
Summary, Conclusions and Recommendations
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(P<0.001) in the studied cases. On the other hand, there was no statistically significant
correlation between AR expression and age (P=0.231), sex (P=0.383) and recurrence (P=0.233).
In regards to the correlation between HER2 and the clinicopathological parameters of the
included cases it was revealed that there was a statistically significant correlation between
HER2 overexpression and higher stage (P=0.001), higher grade (P<0.001) and presence of
lymphovascular invasion (0.045) and there was no statistically significant correlation was found
between HER2 overexpression and age (P=0.209), sex (P=0.240) and recurrence (P=0.897).
Finally, correlation between the two markers was performed and revealed a statistically
significant positive correlation between AR overexpression and HER2 overexpression
(P<0.001).
from the present study it has been concluded that both AR and HER2 overexpression
correlated with higher stage, higher grade and presence of lympohovascular invasion.
Therefore, the evaluation of both markers could be helpful in identifying patients with poorer
prognosis and those that might benefit from therapies targeting AR and anti-HER2 therapies.