الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
It is well known that prostate-specific antigen (PSA) has both advantages and disadvantages as a marker of prostate cancer. Advantages include its ability to effectively detect early-stage prostate cancer and to monitor disease progression. Both prostate cancer cells and normal prostate cells produce PSA; thus, it is frequently increased in nonmalignant conditions such as prostatitis and benign prostatic hyperplasia. The low diagnostic specificity of PSA leads to many false positives and a large number of biopsies in patients who are suspected to have prostate cancer. New prostate cancer biomarkers could play a useful role in reducing the number of unnecessary biopsies.
Previously reported serum EPCA2 appeared to be elevated in many prostate cancer patients, and especially so in patients with more advanced-stages of disease. Preliminary studies have suggested that it may be more accurate than PSA. Currently some clinical trials are still underway to test its accuracy.
The aim of the present work was studying the diagnostic performance (sensitivity and specificity) of serum levels of human early prostate cancer antigen-2(EPCA-2) and prostate specific antigen (PSA)in Egyptian males with carcinoma of the prostate and find its usefulness as prostate cancer markers.
To all the studied subjects in the present work detailed history was taken specially age, smoking index, age of onset of the prostate condition and urinary tract obstructive and irritative symptoms including: frequency, urgency, hematuria and back pain. Also, full clinical,urological and prostatic digital rectal examination was done. Abdominal ultrasonography was done and prostatic tissue biopsy obtained by fine needle aspiration cytology (FNAC) for patients with suspected prostate cancer. Pathological examination was performed to tissue removed by biopsy or radical prostatectomy for benign prostatic hyperplasia(BPH) and prostate cancer (PCa) groups. Clinical staging of carcinoma of prostate was performed in patients with proved prostatic carcinoma.
In addition, laboratory investigations performed to the studied subjects included complete blood picture(CBC), complete urine analysis, determination of serum levels of creatinine as well as serum activities of aminotransferases and alkaline phosphatase. Also, estimation of serum levels of total prostate specific antigen and free PSA and EPCA-2.Free to total PSA ratio and the percent Free PSA were calculated.
There was a significant increase in age (years) when benign prostatic hyperplasia (BPH) (Group2) was compared to control group (Group1) and when prostate cancer (PCa) (Group3) was compared to control group (Group1). This is because the prostate pathology is more frequent with advancing age.
There was a significant increase in smoking index (cigarettes / year)when benign prostatic hyperplasia (BPH) (Group2) was compared to control group (Group1) and when PCa (Group3)was compared to control group (Group1). Also there was a significant increase in smoking index (cigarettes / year) when prostate cancer (PCa) was compared to benign prostatic hyperplasia (BPH) (Group2) confirming that smoking predispose to prostate cancer.
Summary and Conclusion
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There was a significant increase in duration (months) of lower urinary tract symptoms when prostate cancer (PCa) (Group3) was compared to benign prostatic hyperplasia (BPH) (Group2) as PCa usually occurs at an older age with longer duration of symptoms than BPH.
There was a significant decrease in hemoglobin when prostate cancer (PCa) (Group3) was compared to benign prostatic hyperplasia (BPH) (Group2),but the mean is still within reference in agreement that the cancer condition is usually associated with decrease Hb.
There was a significant increase in W.B.Cs when prostate cancer (PCa)(Group3)was compared to control group (Group1),but the mean level is still within reference interval.
There was a significant increase in Ultrasonic volume of the prostate when benign prostatic hyperplasia (BPH) (Group2) was compared to control group (Group1) and when prostate cancer (PCa) (Group3) was compared to control group (Group1) going with that the enlarged size of the prostate was associated with BPH and PCa. In addition, there was a significant increase in Ultrasonic volume of the prostate when prostate cancer (PCa) (Group3) was compared to benign prostatic hyperplasia (BPH) (Group2).
Regarding the prognostic parameters in prostate cancer, by dividing patients according to their age, those having ≤60 years and > 60 years, we found a significant increase in EPCA-2 as increasing in age. However, no change in EPCA-2 regarding to tumor size, nodal involvement nor the presence of metastasis.
There was a significant increase in serum level of creatinine (mg/dl) when prostate cancer (PCa) (Group3), with higher age than controls, was compared to control group (Group1).
There was a significant increase in serum level of AP activities (U/L)when benign prostatic hyperplasia (BPH) (Group2) and prostate cancer (PCa) (Group3) were compared to control group (Group1).
There was a significant increase in serum level of total PSA when both benign prostatic hyperplasia (BPH) (Group2) and prostate cancer (PCa) (Group3) were compared to control group (Group1). Also there was a significant increase in serum level of total PSA when prostate cancer (PCa) (Group3) was compared to benign prostatic hyperplasia (BPH) (Group2). This is going with total PSA increases in the serum of both BPH and PCa.
There was a significant increase in serum level of free PSA when benign prostatic hyperplasia (BPH) group (Group2) and prostate cancer (PCa) (Group3) were compared to control group (Group1).This may be due to high levels of TPSA in these groups.
There was a significant decrease in free to total PSA ratio when prostate cancer group (PCa) (Group3) was compared to both control group (Group1) and benign prostatic hyperplasia(Group2). Also there was a significant decrease in percent free PSA when prostate cancer group (PCa) (Group3) was compared to both control group (Group1) and benign prostatic hyperplasia (BPH) (Group2).
Summary and Conclusion
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There was no significant difference in EPCA-2 between BPH group (Group2) and control group(Group1).
There was a significant increase in serum level of EPCA-2 when prostate cancer group PCa (Group3) was compared to both control group (Group1) and benign prostatic hyperplasia group (BPH) (Group2) pointing that EPCA-2 may be a potential tumor marker for the prostate cancer.
By drawing the ROC curve for TPSA,%fPSA and EPCA-2 in benign prostatic hyperplasia group (BPH) (Group2), the area under the curve (AUC) was0.963(p=0.004), 0.869(p=0.022)and 0.775(p=0.088) respectively, showing that TPSA having the highest AUC.
By drawing ROC curve for TPSA,%fPSA and EPCA-2 in PCa (group 3), the area under the curve (AUC) was 0.994 (p <1.000), 1.000 (p=<1.000) and 0.842 (p=<1.000) respectively. Showing that %fPSA having the highest AUC followed by TPSA then EPCA-2 in PCa patients.
In BPH, using the best cutoff >4.5 ng/ml, TPSA had sensitivity 35%, specificity 100%, PPV 100% and NPV 60.61% and efficiency 67.5%However,EPCA-2,using the best cutoff>21, had better sensitivity 55%, similar specificity100% and PPV 100% and lower NPV 30.77% and efficiency62.5%.
In PCa at the best cutoff >35 ng/ml,the sensitivity of EPCA-2 for PCa was 66.67 %,specificity was 95%, positive predictive value was 96.3%, negative predictive value was 59.4% and clinical accuracy or efficiency was 76.27%. However, the %fPSA at a cutoff ≤7.3 had sensitivity, specificity, PPV,NPP and efficiency 100%for all denoting that %fPSA is the best biomarkers for PCa
By combining of TPSA level at a cutoff of 14.9ng/mL and serumEPCA-2 level at a cutoff of >35 ng/mL in PCa group(Group3),the sensitivity was55% and specificity of 100% with positive predictive of 100%,negative predictive values of 52.63% and efficiency of 70%.the combined marker (TPSA &EPCA-2) is less in efficiency than % FPSA.
In PCa group, in the present study, there was a negative correlation between %fPSA and Gleason score and between EPCA-2 and the ultrasonic volume of prostate cancer.
It could be noticed that the % fPSA level is the most useful biomarker studied for predicting prostate cancer.
It could be concluded:
1. A significant increase in serum level of total PSA when benign prostatic hyperplasia group and prostate cancer group were compared to control group. Also, when PCa group was compared to BPH group.
2. A significant decrease in percent free PSA when PCa group was compared to both control group and BPH group.
Summary and Conclusion
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3. A significant increase in EPCA-2 in patients with age >60years than those ≤60years.
4. A significant positive correlation was found between EPCA-2 and ultrasonic volume of the prostate.
5. For BPH (group 2), the AUC of TPSA was the higher than %fPSA and EPCA-2 and TPSA had the highest clinical accuracy (67.5%) when compared to both EPCA-2 and %FPSA (62.5%,22.5%) respectively.
6. For PCa ( group 3), the AUC of %fPSA was higher than TPSA and EPCA-2 respectively.
7. EPCA-2 could be used as potential serological biomarker to diagnose PCa. EPCA-2 is less efficient as a cancer marker than TPSA and %FPSA respectively with % FPSA showing the highest clinical accuracy.
8. In PCa (group 3), %FPSA at a cutoff≤7.3 ng/ml showed maximum sensitivity, specificity, PPV, NPP and clinical accuracy (100%) for all.