Clinicopathological Study On Biologic Markers For Prostate Adenocarcinoma

ObjectiveIn order to search for new biologic markers as prognostic factors in prostate adenocarcinoma and to provide more information guiding treatment and reducing recurrence and metastasis in clinical practice, the following biologic markers of CK19, NF-κB/P65, FHIT and GSTP1 were investigated, respectively and furthermore, their relevance to tumor biological or clinicopathological characteristics and metastasis of patients were analyzed. Materials and methodsOur study is a retrospective research. One hundred thirty-five cases of prostate adenocarcinomas from 1992 to 2005, in Chinese People's Liberation Army (PLA) General Hospital were collected and reviewed. According to the criteria of Prostate Cancer Histologic Typing of WHO, a total of 50 cases of prostate adenocarcinoma with complete clinical and follow up data were enrolled in the study.Immunohistochemical technique: The four biologic markers—CK19, NF-KB/P65, FHIT and GSTPl expression were detected in 50 cases of paraffin-embedded prostate adenocarcinoma by the standard PV-9000 Polymer Detection System For Immuno-Histological Staining (Zymed, USA), which is the non-biotin HRP detection system to avoid any possible endogenous biotin by heating. Their relationship to clinicopathological featurers as well as prognosis was analysed.MSP: To take advantage of MSP as a main method, we analysed the 5'CpG islands methylation or unmethylation status of GSTPl gene in prostate adenocarcinoma. ResultsThe positive expression rates of biologic markers were as follows: CK1968%(34/50), NF-KB/P65 70%(35/50), FHIT 72%(36/50), GSTPl 18%(9/50). Among them CK19 and FHIT were related to clinical stage and the expression of CK19 and FHIT were found increased corresponding to clinical stage from A to C (P<0.05). The expression of CK19 or FHIT was also correlated with Gleason grade-----the higher expression of CK19 or FHIT, the higher Gleason grade(P<0.05) . NF-KB/P65 and FHIT presented a positive correlation to metastasis. The expression positive ratios of NF-kB/P65 and FHIT in patients with metastasis were higher than those in patients without. The significant differences in expressions of FHIT and GSTPl were found between prostate adenocarcinoma and normal prostate tissue adjacent to carcinoma. The positive expression ratios of FHIT in prostate adenocarcinoma were higher than those in normal tissue(P=0.038 ), while the positive expression ratios of GSTPl were much lower than those in normal tissue (P=0.000) .The seven factors— FHIT, NF-kB/P65, GSTPl, age, clinical stage, Gleason grade and androgen blockage drug treating before radical prostatectomy were showed significant correlation to disease-free survival time in Kaplan-Meier survival analysis. Cox survival analysis demonstrated that NF-kB/P65, age, clinical stage and androgen blockage drug treating before radical prostatectomy were independent prognostic factors for prostate adenocarcinoma. The negative expression of NF-kB/P65, age younger than 65 years, the lower clinical stage, and have androgen blockage drug treated before radical prostatectomy indicated a longer survival time without tumor and better prognosis.The ratio of unmethylation of GSTPl gene promoter in prostate adenocarcinoma was 86% (43/50) by MSP, while none of patients with aberrant promoter CpG islands hypermethylation status of GSTPl gene was found in this group (0/50) of prostate adenocarcinoma, even though MCF-7 as a control was definitely positive. Conclusions: 1. CK19, NF-KB/P65 and FHIT are significantly positive biologic markers ofprostate adenocarcinoma, while GSTPl is a sensitively negative biologic marker of prostate adenocarcinoma.2. The expression of CK19> NF-kB/P65> FRIT is associated with development, invasion and metastasis of prostate adenocarcinoma. It is suggested that increased expression of above-mentioned biologic markers may play an important role in the development and progression of the tumor, and may become new prognostic markers for prostate adenocarcinoma.3. The seven factors—FHIT, NF-kB/P65, GSTPl, age, clinical stage, Gleason grade and androgen blockage drug treating before radical prostatectomy were all showed significant correlation to disease-free survival time of prostate adenocarcinoma. NF-kB/P65, age, clinical stage and androgen blockage drug treating before radical prostatectomy were independent prognostic factors for disease-free survival time of prostate adenocarcinoma.4. It is suggested that GSTPl plays an important role in the genesis and progress of prostate adenocarcinoma and the loss of GSTPl expression may become a new adjunct diagnostic marker in prostate adenocarcinoma .The absent expression of GSTPl probably has no relationship with GSTPl gene promoter CpG islands methylation in Chinese patients with prostate adenocarcinoma, however, it remains to be further clarified by more studies.