Correlation of angiogenesis with grade and recurrence in superficial and invasive urinary bladder transitional cell carcinoma

ABSTRACT

The aim of this study was to correlate the level of MVD with the grade, recurrence and prognosis of the tumor in an attempt to understand the events controlling angiogenesis so as to evaluate the use of anti-angiogenic therapy in the treatment of urinary bladder tumours. The material of this study consisted of 52 selected PT1 and PT2 cases of transitional cell carcinoma [TCC] obtained by transurethral resection biopsy. Cases were collected from El-Sahel teaching hospital during the period from Januray 2006 to January 2009. Age, sex and other clinical data of the patients were taken from the clinical sheets. Each paraffin block was re-cut by microtome at five Um thickness,stained with haemtoxylin and eosin for routine histopathological examination and grading of the tumour and assessment of muscle invasion. Immunohistochemical staining of the endothelial cells was done by monoclonal antibody against CD31 antigen. 32 cases were superficial TCC while 20 were invasiveTCC. Superficial TCC cases were treated starting 2 weeks after TURBT by intravesical Bacillus Calmete and Guerin [BCG] in 28 out of the 32 cases of superficial TCC. All cases went under follow up for a period of 24 months,however,only 30 cases showed regular follow up. Six cases showed recurrence of the tumour after a follow-up period ranging from 20 - 24 months.Invasive TCC cases were treated by radical cystectomy and urinary diversion with follow up every 6 months, however, pelvic nodules were seen in 4 cases after 2 years. Histopathological evaluation was done for grade of tumour and the extent of invasion,counting the neovascular density after immunostaining by monoclonal antibody against CD31 antigen to determine the MVD. The age of Jhe patients in all studied cases ranged from 30 to 79 years with 41 males and 11 females.Of the 52 studied cases,32 [61.5%] were stage pTl, while 20 cases [38.5%] were stage pT2. Grades 1,2,3 were respectively found in 18,30 and 4cases. All grade 1 cases were stage pTl [100%], while grade 2 cases showed 14 cases [46.6%] stage pTl and 16 cases [53.4%] stage pT2. All grade 3 cases were stage pT2 [100%]. Six cases showed recurrence after treatment; 2 were grade 1 and 4 were grade 2. All recurrent cases were stage pTl,2of them showed bilharzial infestation and were grade 2.MVD was counted per high power field [HPF] at magnification x400The median MVD in grade 1 cases was 37 vessels/HPF In grade 2 cases it was 53.5 vessels/HPF ,some of which were superficial tumours ,while others were invasive .In grade 3 cases it was 116.5 vessels/HPF .According to the stages of the studied cases of TCC, MVD ranges in stage pTl,pT2 and pT3 cases were 19-88,39-148 and 116.5vessels/HPF.The median MVD of stage pTl grade 1 cases was 37 vessels/HPF, median MVD in stage pTl grade 2 cases was 53.5 vessels/ HPF, while stage pT2 grade 2 cases was 68.5 vessels/HPF. As for grade 3, all cases were stage pT2, the median MVD was 116.5 vessels/HPF. The median MVD is increasing as the grade increases [P <0 .001]. The median MVD for grade 1 cases showing recurrence was 46, and grade 2 cases showing recurrence was 53.5, while grade 1 cases without recurrence was 36 and grade 2 was 57. Out of the 52 cases,there were 6 cases of recurrence;3 cases were within a MVD range 0-50,another 3 cases were in the MVD range 51-100 while there were no cases of recurrence found in the MVD range over l00.The remaining 46 cases without recurrence were 22 cases in a MVD range 0-50, 21 cases in the MVD range 51-100 and 3 cases in the MVD range above 100. Tumor grade and MVD are valuable to predict prognosis in superficial TCC while quantification of angiogenesis does not help in the prediction of the recurrence in superficial TCC. Moreover,a significant correlation was found between MVD and tumour grade for stages PTl and PT2.Thus,MVD correlation with tumour grade can help in planning for anti-angiogenesis strategies. We recommend to further study the effect of anti-angiogenic treatment as a curative modality together with the routine therapeutic regimen for grades 2 and 3