Investigation Of B7H3 In Benign And Malignant Renal Tumors And Their Angiogenesis

ObjectiveCell surface molecule B7H3 has different expression patterns in a variety of tissues and cancer types;it can also distinguish pathological and physiological angiogenesis.Our purpose was to investigate its expression in benign and malignant renal tumors and their angiogenesis,and to explore its possible values in clinical practice.MethodsFrom July 2006 to August 2008,31 consecutive renal angiomyolipoma(AML) with no history of tuberous sclerosis received surgical treatment in our department.By immunohistochemistry,we compared B7H3 expression patterns in paraffin-embedded specimens,between them and another 31 pathological tumor size paired clear cell renal cell carcinomas(RCC);paired normal renal parenchyma from each of the patients above as well as 4 corpus luteum specimens were also analyzed.Of the selected AML and RCC patients,11 serum samples for each group were extracted from our tissue bank,and the concentration of peripheral blood(PB) soluble B7H3(sB7H3) was detected and compared by enzyme-linked immunosorbent assay(ELISA).Prospectively,twenty PB samples were collected before operation,including 2 from renal cysts,one from incision infections after radical nephrectomy,one from local recurrence of papillary RCC,four from metastatic RCC,as well as one from locally advanced RCC,and the other 11 from renal tumors with difficulty in deciding their malignancy only by radiological study.PB B7H3 mRNA level were analyzed using real-time PCR,and compared with the postoperative pathological results.All tissue and PB samples' collection and use were in line with the Helsinki Declaration of Human Rights.Results1,Cancer cell expression of B7H3 was found in 22.6%(7/31) of clear cell RCCs,but that of tumor vessels was confirmed in all the 31 cases;focal, moderate and diffuse expression of the tumor vessels in RCCs were 3/31,7/31, and 21/31,respectively;no obvious positive expression was detected in either tumor cells or tumor vessels of renal AML,neither in the 62 paired normal renal parenchyma and their vessels;four cases of luteal blood vessels do not express B7H3,but all the theca folliculin cells were positive for B7H3.2,Serum concentration of sB7H3 from RCC and AML were:16.47ng/ml and 16.31ng/ml,with no significant difference(p＞0.05);sB7H3 had no significant correlation with tumor and blood vessels expression of B7H3(p＞0.05).3,Forty-five cycles of the real-time PCR found four cases with no detectable B7H3 mRNA,of which 2 were simple cysts,and the other 2 AMLs;after normalized,we found minimal level of B7H3 mRNA in PB.The renal AML group had similar B7H3 mRNA level with the normal control(renal cysts and incision infections)(p＞0.05),and significantly lower than the RCC group(p＜0.001); there was no difference between RCCs of different types or tumor size in localized ones(p＞0.05);the level of PB B7H3 mRNA in non-metastatic RCCs was slightly lower than that of metastatic RCCs,although without significant difference(p＞0.05).Conclusion1,A small group of clear cell RCC expressed B7H3 in tumor cells,while tumor cells of renal AML did not express B7H3,and we happened to find theca folliculin cells in the corpus luteum also had expression of B7H3.2,B7H3 selectively expressed in angiogenestic endothelial cells of RCCs,but not in that of AMLs,nor in normal or physiological angiogenestic endothelial cells.3,Serum concentration of sB7H3 from clear cell RCCs and AMLs had no difference in between,and seemed similar to that from normal adult.4,B7H3 mRNA levels in PB could distinguish AML from RCCs,when radiological study confirmed a renal tumor but had difficulties in differential diagnose.Specific expression in malignant blood vessels and some cancer cells made B7H3 a potential role not only in tumor and angiogenesis-targeted therapies,but also in tumor vessel based differential diagnose.