الفهرس 
I. INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Prostate carcinoma is one of the most common malignant neoplasms
worldwide and a significant cause of cancer-related morbidity and mortality. The
great variability of tumor behavior constitutes a major issue for clinical management
of this disease. The current trend of world population ageing strongly suggests that the
medical burden of this disease will become increasingly important in the near future.
In order to face this challenge it is essential to deepen the knowledge of the molecular
mechanisms of prostate carcinogenesis and also to find novel genetic biomarkers with
prognostic value.
In this study, the aim of this work was to verify the association of prostate
cancer with detection in blood of TMPRSS2:ERG gene fusion, PCA3, PSA gene
expressions and investigated how these biomarkers may be combined with serum
PSA levels to develop clinically practical algorithms for predicting prostate cancer
diagnosis.
. To fulfill this aim, 90 subjects were submitted to this study divided into three
groups: group I: included 30 healthy volunteers clinically free from any disease their
mean age was (63.80 ±3.58) years, group II: included 30 benign prostatic hyperplasia
patients, their mean age was (61.70 ±3.71) years and group III: included 30 prostatic
cancer patients, their mean age was (63.60 ±4.20) years. Patients in group II and III
were of matched age as the control group and were recruited from the Gamal Abd El-
Nasser Hospital, Alexandria branch. An informed consent was taken from all
contributors in this study. This work was conducted according to the guidelines of the
local Ethical Committee of MRI.
To all subjects the followinginvestigations were done:- 1- full history
recording, 2- Routine laboratory investigations including complete blood picture
”CBC”, urea, creatinine, ALT and AST, 3- Determination of: a) serum prostatespecific
antigen (PSA) and b) RT-PCR for PSA, PCA3 and TMPRSS2:ERG gene
expressions.
The experimental results revealed that:
Age distribution (years) in male patients groups with either BPH or PCa was
insignificantly different than in male control group.
The level of serum PSA (mg/ml) in male patients groups with either BPH or
PCa was significantly higher than in male control group
(P2=<0.001,P3=<0.001). Also, levels of PSA in PCa group of patients was
higher than BPH group of patients and showed significant difference
(p1=<0.001).
In both groups of patients, the mean values of serum AST concentration (U/l)
(P=0.064) and serum ALT concentration (U/l) (P= 0.086) were insignificantly
higher than in control group.
In both groups of patients, the mean values of serum urea concentration(mg/dl) (P=0.163) and serum creatinine concentration (mg/dl) (P=0.806) were
insignificantly higher than in control group.
The mean value of WBCs count, MCH, MCHC and MCV in both groups of
patients were insignicantly higher than in control group (P= 0.702). While
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MCH, MCHC and MCV in both groups of patients were insignicantly lower
than in control group (P= 0.702, P= 0.875, P= 0.918 and P= 0.333,
respectively). Also, Platelets count, RBCs count, Hb and HCT, and
concentration in both groups of patients were significantly less than in control
subjects (P=<0.001, P=<0.001, P=<0.001 and P= 0.028, respectively).
The ROC curve analysis was used to compare the diagnostic values of PSA,
PCA3 and TMPRSS2:ERG gene expressions by RT-PCR in all study subjects
depending on the area under the curve (AUC). The higher AUC corresponds
to a better diagnostic test. The curve showed that TMPRSS2:ERG fusion gene
was excellent diagnostic markers of prostatic disease followed by PCA3 gene
and PSA gene respectively as was indicated by asymptomatic significance and
very high area under the curve. (TMPRSS2:ERG-mRNA gene expression
showed significant AUC (0.924), P (<0.0001) with sensitivity (89.66%) and
specificity (95.08%). PCA3-mRNA gene expression showed significant AUC
(0.856), (P<0.0001) with sensitivity (82.76%) and specificity (88.52%). PSAmRNA
gene expression showed significant AUC (0.746), (P P<0.0001) with
sensitivity (68.97%) and specificity (80.33%)).