Correlative Study Of Angiogenesis And PCNA With The CT Multi-Phase Scan Features Of Benign Prostatic Hyperplasia And Prostate Cancer

Objective To investigate the relationship of MVD,related indexes of microvascular,vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),proliferating cell nuclear antigen(PCNA),and the clinicopathologic characters of benign prostatic hyperplasia(BPH) and prostate cancer(PCa).To explore the correlation between the multi-phase multi-slice computed tomography(MSCT) imaging features and the level of MVD,VEGF,bFGF,PNCA and related indexs of microvascular of BPH and Pea.Materials and Methods Thirty-five BPH and twenty-seven PCa cases proved by histopathology were examined with multi-phase contrast-enhanced MSCT scanning before operation or biopsy.The slice of biggest lesion was taken as middle slice,and then multi-phase MSCT scanning was performed at different time such as 25s,30s, 35s,40s,75s and 180s after a bolus injection of iodinated contrast medium by elbow vein(1.5ml/kg body weight,the injection rate,3.0 or 3.5ml/s).Four slices were collected at a time.the thickness of a slice was 6mm or 8mm,the cover range was 24mm or 32mm.The MSCT imaging features of BPH and PCa in different phases were analyzed:Several regions of interest(ROIs) were selected to measure CT value of the lesions of BPH and PCa,and then the time-density curve(T-DC) was obtained. Three types of the curves were classified accoding to the shapes.There were three types of curves including typeⅠwhich had steady enhancement:typeⅡ,slowly ascending and slowly descending of the enhancement;typeⅢ,fast ascending and fast descending.The peak value(PV),maximum attenuation value(MAV) and time-density curve were recorded.All specimens were fixed in 10%neutral buffered formalin and paraffin embedded completely,and consecutive sections made with a 4μm-thickness on which HE staining and S-P immunohistochemical technique were experimented.The CT features,clinicopathologic features and the level of MVD, VEGF,bFGF,PNCA and related indexs of microvascular were analyzed to investigate the relationship with each other.Results Accoding to the clinicopathologic stage of PCa,stage B,C and D was 13, 9 and 5 cases respectively.Well-differentiated carcinoma cases were 7,moderately and poorly differentiated were both 10.The Gleason grade was 3～10(mean 6.26±2.44).The results of multi-phase scan of MSCT:The peak value of 71.43% (25/35) BPH was seen in delayed phase(180s),28.57%(10/35) in venous phase(75s); the peak value of 70.37%(19/27) PCa was in late arterial phase(35～40s) and in venous phase,29.63%(8/27) in delayed phase,there was significant difference between BPH and PCa(P＜0.01).The time-density curves were classified three types according to their shapes:In the group of BPH,typeⅠcould be seen in 25 cases,typeⅡin 10cases;In the group of PCa,typeⅠin 8 cases,typeⅡand typeⅢin 10 and 9 cases.The difference between BPH and PCa in the type of the curves was observed (x~2=17.009,P＜0.01).The maximum attenuation value(MAV) of BPH and PCa was 44.06±10.26HU and 46.78±11.14HU respectively,there was no difference between them(P＞0.05).The immunohistochemical results:The number of MVD in BPH and PCa was 11.00±4.14 and 32.11±13.19 respectively,the later was obviously higher than the former(P＜0.01).and the related indexs of microvascular of BPH such as diameter was bigger than that of PCa(P＜0.001).The expression of VEGF in BPH was mainly -～+(24/35),but in PCa was mainly ++～+++(20/27),there was difference between them(x~2=11.088.P＜0.001);The expression of bFGF in BPH was mainly -～+(30/35).but in PCa was mainly ++～+++(15/27).the difference between them was significant(x~2=11.880,P＜0.01).The expression of PCNA in BPH was mainly 1～2 grade(32/35),but in PCa was mainly 3～4 grade(20/27),the difference between them was found(x~2=31.113,P＜0.01).The level of VEGF,bFGF,PCNA in PCa was higher.The analysis of correlation:In BPH group,there was significant positive correlation between VEGF,bFGF and MVD(r=0.805,0.612;P=0.000, 0.001),and between MAV and MVD,VEGF,bFGF(r=0.647,0.500,0.389;P=0.000, 0.002,0.021),and between VEGF and bFGF(r=0.636,P=0.000);However,there was no correlation between PCNA and VEGF,bFGF,MVD,MAV.In PCa group,A positive correlation was observed between VEGF,bFGF and MVD(r=0.590,0.528; P=0.001,0.005),and between VEGF and bFGF(r=0.545,P=0.003);There was significant positive correlation between PCNA and Gleason grade,differentiation of the tumor,clinical stage(r=0.632,0.608,0.438;P=0.000,0.000,0.022),but no correlation with VEGF,bFGF,MVD;A positive correlation was found between VEGF and Gleason grade,differentiation of the tumor(r=0.550,0.541;P=0.003, 0.004),but no correlation with clinic stage(r=0.238,P=0.232);There was positive correlation between MVD and Gleason grade,differentiation of the tumor(r=0.530, 0.509;P=0.004,0.007);but no correlation with clinic stage(r=0.221,P=0.267);A positive correlation between MAV and bFGF,MVD was observed(r=0.384,0.665; P=0.048,0.000),but no correlation with PCNA and VEGF;However,there was an increasing trend of MAV following a higher expression;There was no correlation between MAV and related indexs of microvascular,Gleason grade,differentiation of the tumor,clinical stage.Conclusion The level of PCNA,bFGF,VEGF and MVD in PCa was higher than in BPH,but the related indexs of microvascular of BPH as diameter was bigger than that of PCa.Prostate cancer is a tumor with abundant blood supply;MSCT can reflect the blood supply and enhancement characters of BPH and PCa.it has significance in detection and diagnosis of the prostate carcer lesions.This study shows the MSCT features of BPH and PCa are correlated with the level of VEGF,bFGF and MVD.The MSCT imaging of BPH and PCa can indicate the level of VEGF,bFGF and MVD to some extent.It will be beneficial to the early diagnosis and helpful to the therapy plan.