Ekspresija proangiogenih faktora vaskularnog endotelnog faktora rasta i matriks metaloproteinaze- 9 i njihova povezanost sa angiogenezom u karcinomu prostate
Expression of the proangiogenic factors, vascular endothelial growth factor and matrix-metalloproteinase-9, and their correlation with angiogenesis in prostate carcinoma
Članovi komisijeEri, Živka
MetapodaciPrikaz svih podataka o disertaciji
The increased early detection and subsequent radical surgery of prostatic cancer has prompted the search for methods and markers applicable to the initial core biopsy specImens and predictive for pathological stage and disease outcome. More than 15 prcents of men with clinically localized prostate cancer who are treated by pelvic lymph node dissection and radical prostatectomy (RP) are understaged using established preoperative clinical and pathologic results. Although parameters like histological grade, PSA serum levels, clinical staging or DNA ploidy have been shown to correlate alone or in combination with the final pathological stage, they are inaccurate and inappropriate on an individual basis. Additional biomarkers are needed to increase the predictive accuracy for pathologic stage, but each must be evaluable from a needle core biopsy core with cancer, recognizing that this is the only tissue specimen obtained from patients who are not treated surgically. Angiogenesis is believe...d to play an important role in tumor progression and metastasis. The study population included sixty-one patients who underwent radical prostatectomy (RP) for clinically localized prostate carcinoma and did not receive chemo-, hormone, or radiation therapy before surgery. Predictive value of microvessel density (MVD) and proangiogenic factors, vascular endothelial factor (VEGF) and matrix-metalloproteinase-9 (MMP-9), was evaluated in combination with Gleason score and preoperative serum PSA concentration, for extraprostatic extension. The neovascularization of prostatic adenocarcinomas in core biopsies and corresponding prostatectomies was investigated on totally embedded, serially sectioned prostate tissues. Normal prostate tissue generally showed no or only low VEGF and MMP-9 expression, there was a significant increase in VEGF and MMP-9 expression in almost all prostate cancer specimens, the intensity of the immunoreaction ranging from low to strong and being correlated positively with the tumor stage (VEGF: p < 0,0001; MMP-9: p < 0,05). Gleason score (VEGF and MMP-9: p < 0,001) and MVD (VEGF: p 0,05: MMP-9: p < 0,001) in prostate carcinoma. Patients who had stronger expression VEGF in prostate carcinoma tissue, also had stronger expression of MMP-9 (p < 0,05). There was no correlation between VEGF and MMP-9 expression and preoperative serum PSA (p > 0,1). These results showed that stronger expression of VEGF I MMP-9 and higher MVD were present in organ - extending prostate carcinoma (pT3). and in metastatic disease (pN1), and also in tumors with higher Gleason score (GS?7), confirming a role of angiogenesis, cell cohesion and invasion in metastatic spread of disease.