Abstract: The Relationship between Upregulation of NGAL and Tumorigenesis of the ColorectumHui LI1, Baocun SUN1,2, Zhiyong LIU1, Xiulan ZHAO2, Yan SUN1, Lihua ZHANG1, Xueyi DONG2, Lisha QI1Correspondence to: Baocun SUN, E-mail: baocunsun@eyou.com1Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China2Teaching and Research Section of Pathology, Tianjin Medical University, Tianjin 300070, ChinaThis work was supported by National Natural Science Foundation of China (No. 30830049) and Sino-Swiss International CooperationProjects (No. 09ZCZDSF04400)Abstract Objective: To investigate the expression and relationship of neutrophilic granulocyte gelatinase-associated-lipocalin (NGAL ) and matrix metalloproteinase-9 ( MMP-9 ) in the colorectal adenoma-carcinoma sequence, and to evaluate their role in the inci-dence of colorectal carcinoma. Methods: The expression of NGAL and MMP-9 proteins were detected using tissue microarray and S-Pimmunohistochemical methods in 94 cases with formalin-fixed, paraffin-embedded normal paraneoplastic mucosa which were near ade-noma or carcinoma, 92 cases with adenoma (including 36 with tubular adenoma, 47 with tubulovillous adenoma, and 9 with villous ade-noma ), 54 cases with adenoma of atypical hyperplasia, and 60 cases with colorectal adenocarcinoma. Results: The positive expressionrates of NGAL protein were 55 % ( 33/60 ), 37 % ( 20/54 ), 23 % ( 21/92 ) and 2 % ( 2/94 ) in colorectal adenocarcinoma, adenoma ofatypical hyperplasia, adenoma, and normal tissue adjacent to the adenoma or carcinoma, respectively. The positive expression rates ofMMP-9 protein were 74 % ( 44/60 ), 44 % ( 24/54 ), 25 % ( 23/92 ), and 6 % ( 6/94 ) in the aforementioned tissues, respectively. The ex-pression of NGAL and MMP-9 proteins was significantly higher in the adenocarcinoma, adenoma of atypical hyperplasia, and adenomathan in the normal paraneoplastic tissue. There were statistical differences among these groups ( P < 0.01 ). The expression of NGALand MMP-9 proteins increased gradually during the procession from normal mucosa, adenoma and adenoma of atypical hyperplasia tocolorectal adenocarcinoma. There were statistically significant differences among the groups ( P < 0.01 ), while there were no statisticaldifferences among tubular adenoma, tubulovillous adenoma and villous adenoma ( P > 0.05 ). There was a significant positive correla-tion between the expression of NGAL and MMP-9 proteins during the adenoma-carcinoma sequence ( including normal mucosa of thelarge bowel, adenoma, adenoma of atypical hyperplasia, and adenocarcinoma ) ( rs = 0.622, P < 0.01 ). Conclusion: The upregulated ex-pression of NGAL and MMP-9 proteins may play a role in the colorectal adenoma-carcinoma sequence, and the abnormal expression ofthe two proteins may be important in the carcinogenesis of colorectal adenocarcinoma.Key words Neutrophilic granulocyte gelatinase-associated lipocalin; Matrix metalloproteinase-9; Large bowel;Adenocarcinoma; Adenoma