The Role Of NGAL And Its Receptor In Colorectal Adenoma-carcinoma Sequence And Angiogenesis

ObjectiveCompare the difference of the expression of Neutrorphil gelatinase-associated-lipocalin (NGAL) and its receptor (NGALR) in normal mucosa of the large intestine,colorectal adenoma(including tubular adenoma,tubulovillous adenoma and villous adenoma),adenoma with atypical hyperplasia and colorectal adenocarcinoma.To detect the expression of Matrix metalloproteinase-9 (MMP-9) and Vascular endothelial growth factor (VEGF) by immunohistochemistry and count Microvessel density (MVD) of these samples evaluated by immunohistochemical of CD34.Compare the relationship between the expression of NGAL,NGALR and MMP-9,VEGF,CD34,and approach the role of NGAL and NGALR in tumorigenesis and angiogenesis of colorectal carcinoma.Methods1.Two hundred and six cases with definite pathologic diagnosis in Tianjin Medical University Cancer Institute and Hospital from January 2000 to december 2008 were collected in this study. All specimens consisted of thirty six cases of tubular adenoma,forty seven cases of tubulovillous adenoma, nine cases of villous adenoma,fifty four cases of adenoma with atypical hyperplasia,and sixty cases of colorectal adenocarcinoma, respectively. Additionally, their were ninety four normal tissues which more than 5cm away from the adenoma or carcinoma were collected for control. The H&E-stained sections of every specimen was observed again and checked the pathologic diagnosis by salty pathological doctor and tissue microarry was made.2.To detect the difference of the expression of NGAL and NGALR in different phases of the colorectal adenoma-carcinoma sequence using immunohistochemistry, investigate clinical pathological significance and analyze their role in the colorectal adenoma-carcinoma sequence.To detect the expression of Matrix metalloproteinase-9 (MMP-9)and Vascular endothelial growth factor(VEGF),count Microvessel density(MVD) of these samples evaluated by immunohistochemical of CD34. Compare the relationship between the expression of NGAL,NGALR and MMP-9,VEGF,CD34 and approach the role of NGAL and NGALR in angiogenesis of colorectal carcinoma.Results1. The expression of NGAL and NGALR and clinical pathological significance in different phases of the colorectal adenoma-carcinoma sequence.The expression rate of NGAL in colorectal adenocarcinoma, adenoma with atypical hyperplasia,adenoma,and adjacent mucosa were 55%(33/60),35% (19/54),23%(21/92) and 2%(2/94) respectively. The expression rate of NGALR in colorectal adenocarcinoma, adenoma with atypical hyperplasia,adenoma,and adjacent mucosa were 62%(44/60),46%(24/54),28%(23/92) and 9%(9/94) respectively. There were significant statistical differences between colorectal adenocarcinoma, adenoma with atypical hyperplasia, adenoma and adjacent mucosa (P<0.05).From normal mucosa, adenoma, adenoma with atypical hyperplasia to colorectal adenocarcinoma, the expression of NGAL and NGALR increased gradually.And there were significant statistical differences (P<0.05).While there were no significant statistical differences between tubular adenoma,tubulovillous adenoma and villous adenoma (P>0.05)The expression of NGAL was associated with age,size and type in adenoma, was associated with age,size,site,the degree of atypical hyperplasia in adenoma with atypical hyperplasia, was associated with tumor site,grade,stage,recurrence and metastasis in colorectal carcinoma. The expression of NGALR was associated with size,number in adenoma, was associated with site in adenoma with atypical hyperplasia, was associated with gender, tumor lymph node metastasis, recurrence and metastasis in colorectal carcinoma.2. The expression of MMP-9,VEGF and CD34 in different phases of the colorectal adenoma-carcinoma sequenceThe expression rate of MMP-9 in colorectal adenocarcinoma, adenoma with atypical hyperplasia,adenoma,and adjacent mucosa were 74% (44/60),44% (24/54),25%(23/92) and 6%(6/94), respectively. The expression rate of VEGF in colorectal adenocarcinoma, adenoma with atypical hyperplasia,adenoma,and adjacent mucosa were 75%(45/60),45%(24/54),41%(38/92) and 29%(27/94), respectively.The MVD were (34.16±10.347), (24.38±5.327), (21.15±7.228) and (13.90±3.700), respectively. There were significant statistical differences between colorectal adenocarcinoma, adenoma with atypical hyperplasia, adenoma and adjacent mucosa (P<0.05).From normal mucosa, adenoma, adenoma with atypical hyperplasia to colorectal adenocarcinoma, the expression of MMP-9,VEGF and CD34 increased gradually.And there were significant statistical differences (P <0.05).While there were no significant statistical differences between tubular adenoma,tubulovillous adenoma and villous adenoma of the three proteins. (P>0.05).3. There was positive correlation among the expression of NGAL,NGALR, MMP-9 and VEGF across the hole adenoma-carcinoma sequenc(P<0.05). Although no correlation between NGAL,NGALR,MMP-9,VEGF and MVD was found (P>0.05).Conelusions1.The overexpression of NGAL and NGALR may play a role in the colorectal adenoma-carcinoma sequence.Their abnormal experssion may participate in the tumorigenesis of colorectal carcinoma,and play a role in tumor progression by promoting recurrence or metastasis.2. During the hole colorectal adenoma-carcinoma sequence the abnormal experssion of NGAL and NGALR parallel to the upregulation of MMP-9,VEGF,and MVD increasing of local tissues. They may play an indirect role in the angiogenesis of colorectal tumor,while not the direct triggering of angiogenesis.The mechanism is not yet farther studied.