الفهرس 
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Abstract
P
rostate cancer (PC) is one of the most common cancers in men worldwide. The early detection of PC hand in hand with accurate staging is very important issue in the follow up and managing patients with PC and is associated with an improved outcome.
Radical prostatectomy is the most reliable treatment for patients with organ confined PC, 30% of these patients will fail treatment. This is often attributable to early disseminations of microscopic metastatic disease.
Serum PSA, DRE, bone scan finding and CT scan are current preoperative staging modalities which are available to clinicians, but are poor predictors for extracapsular disease.
Search for valuable marker to discriminate PC patients remains the main issue for clinical research.
Prostate specific antigen (PSA), one of the kallikrein family, in the serum is the most widely accepted marker for monitoring patients with PC. However, serum PSA has many limitations, as it may also be driven by certain non-malignant causes such as nodular hyperplastic changes in the prostate gland and prostatic inflammatory processes and misses a significant number of cancers at cutoff-point 4.0 ng/mL.
Human kallikrein 2 (hk2) is another member of the human kallikrein family. It has the highest homology to PSA (hK3) with about 80% identity at the amino acid level. In addition, hk2 shows a role in the regulation of PSA activation through its ability to convert the pro-PSA form into mature PSA.
Immunohistochemical studies have shown an incremental increase in hk2 expression from benign epithelium, to prostatic intraepithelial neoplasia, to PC. This property of hk2 suggests that KLK2 mRNA as an RT-PCR target for discriminating PC patients and the detection of circulating PC cells, which in turn may correlate with both occult micrometastasis disease and the risk of disease progression.
The aim of the present study was to assess the use of RT-PCR for KLK2 mRNA for discrimination of PC patients in peripheral blood. It was also necessary to assess serum PSA (total, free and f/t PSA ratio) and to compare its results with KLK2-mRNA.
This study included two subject groups; a control group (n=20) and patients’ group (n=25). The control subjects in this study were patients suffering from benign prostatic hyperplasia (BPH). In the present study patients’ group were divided into three subgroups: prostatic intraepithelial neoplasia (PIN) (n=4), localized PC subgroup (n=15) and metastaic PC subgroup (n=6). For all subjects, serum tPSA, fPSA and f/t PSA ratio were measured by immunometric chemiluminescent method using the reagent product of DPC, on ”Immulite System”. Detection of KLK2-mRNA in the peripheral blood was also performed for all subjects included in the study, using RT-PCR method after RNA extraction. Both RNA extraction and RT-PCR were performed using ”QIAGEN” reagents. For PC patients, clinical and radiological assessments, as well as histopathological examination of lesions were performed to confirm the diagnosis.
Our results showed that serum tPSA concentration was significantly increased in non metastatic PC subgroup and metastatic PC subgroup compared to BPH patients and also it showed statistically significant increase in metastatic PC patients versus non metastatic PC patients. While, f/tPSA ratio showed no statistically significant difference between different PC subgroups and control one or between metastatic subgroup and non metastatic one. Also, the ratio could not differentiate between low grade tumor and high grade tumor.
Concerning KLK2 mRNA, our results were presented as percent positivity. As regards the control group, (subjects with BPH) all cases showed KLK2 mRNA negative results. KLK2 mRNA percent positivity was greater in PC patients compared to BPH. Also, KLK2 mRNA percent positivity significantly increased from zero in BPH group to 88.9% of eight PC patients having their PSA results in the gray zone.
When studying the relation between KLK2 mRNA and tPSA value, in gray zone and >10 ng/mL, in PC patients, this study revealed absence of a significant relation between circulating KLK2 mRNA positivity and tPSA levels or f/tPSA ratio in PC patients using a cutoff <0.15 for diagnosis of PC.
According to the pathological staging and grading KLK2 mRNA percent positivity showed no relation to presence or absence of metastasis nor to different tumor grades in PC patients.