TURKISH JOURNAL OF UROLOGY, sa.2, ss.162-167, 2006 (ESCI)
Introduction: Prostate cancer is the most commonly diagnosed cancer among men in the world. Primary options for treatment include observation only, hormonal ablation, radiation therapy, and radical prostatectomy. Prostate carcinoma detection has been increased with the use of prostate specific antigen. Successful attempts were made to establish useful prognostic factors for the outcome of prostate carcinoma, like TNM stage, Gleason's grade and serum PSA level. However despite current clinical, serologic and radiologic evaluations of patients, as many as 30% of patients are found to have disease that has penetrated the capsule and/or seminal vesicles on final pathologic analysis after radical prostatectomy. Various new prognostic factors that have been suggested to provide additional prognostic information include proliferative activity, overexpression of the apoptosis-inhibiting oncogene Bcl-2, neoangiogenesis and inactivation of the P53 tumor suppressor gene. Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The goal of this study was to evaluate of histopathologic parameters and neoangiogenesis in men undergoing radical prostatectomy. Materials and Methods: We analyzed between 1996 and 2002, 40 consecutive patients with prostate cancer who underwent lymphadenectomy and radical prostatectomy (RP). The patients who qualified for the study had a preoperative serum PSA level, age, preoperative histologic grade according to the Gleason histological scoring system and the other prognostic histopathologic parameters (surgical margin of resection, extraprostatic extent of cancer, lymph node metastases and seminal vesicle involvement) and microvascular density (MVD) in RP. Cases were categorized into groups of s-PSA < 4 ng/ml, 4.1-10, 10.1-20 and greater than 20. All prostate biopsies were reviewed and Gleason score, percent cores positive for carcinoma, and perineural invasion were recorded for each specimen. Positive surgical margins were those showing tumor in the shave bladder neck tissues, in distal urethral shave tissues, or in the inked edges of the remaining portions of the RP. Seminal vesicle invasion was defined as infiltration of the muscular coat of one or both seminal vesicle. Invasion of the periprostatic soft tissue was defined as extraprostatic extention. The hematoxylin-andeosin-stained slides (needle biopsy and radical prostatectomy) were examined, and the tumors were graded by assigning both a primary and secondary Gleason score. A single representative block from each prostate specimen was selected and 3 micron thick sections were used for the CD 34 immunostaining. Microvascularity density quantification was performed using CD 34 antigen immunohistochemistry as previously defined. All slides were evaluated for immunostaining in a blinded fashion without any clinicopathologic data. The immunoreactivity was evaluated at 400x magnification and 10 most vascular areas were assessed. Any positive cell or cell cluster, clearly separate from adjacent microvessels, tumor cells and other connective tissue elements, was considered a single, countable microvessel. Microvessel density was then recorded as the mean of 10 high power fields. We used the Pearson correlation test, chi-square test and Mann-Whitney U test for statistic analysis. Results: The mean age was 65.5 years (range: 57-73). Serum PSA ranged from 2 to 58 ng/ml. The mean MVD for CD 34 ranged from a minimum of 28 to a maximum of 180. We were able to demonstrate a high degree of correlation between microvascularity in radical prostatectomy and that in the corresponding involvement seminal vesicle and extraprostatic extention. MVD was not significantly associated with Gleason grade in RP specimens in this study. Conclusion: Angiogenesis is essential for tumor growth and metastasis and has been proposed as a marker for tumor aggressiveness in several cancers. Angiogenic factors can be secreted by tumor cells, inflammatory cells and stromal cells. Histological evaluation of MVD in prostatic adenocarcinomas may improve the prediction of involvement of seminal vesicle and surgical margins. Additional data defining the positive predictive value of MVD and its relationship to other preoperative and postoperative parameters can provide a useful addition to our staging procedures. Obviously larger series may provide information that can help predicting the effectiveness of therapy in a particular patient.