title: Matrix metalloproteinase-9 expression in the normal mucosa-adenoma-dysplasia-adenocarcinoma sequence of the colon.
abstract: It has been proposed that matrix metalloproteinases (MMPs) play a role in tumor invasion. We determined protein expression of matrix metalloproteinase-9 (MMP-9) in colorectal cancer (CRC), corresponding normal mucosa and colorectal adenomas. For confirmation of immunohistochemical results MMP-9 TaqMan RT-PCR analysis was performed. Expression of MMP-9 was determined on paraffin embedded biopsy sections by immunohistochemistry in 31 CRC patients (from cancer tissue and corresponding normal mucosa) and in 30 patients with adenoma (nine adenomas with high grade of dysplasia). MMP-9 immunostaining was determined semi-quantitatively. For Taqman RT-PCR analyses normal mucosa (n = 5), adenoma without (n = 6) and with high grade dysplasia (n = 7) and CRC (n = 10) were investigated. Statistical analysis with ANOVA, LSD test and correlation analysis were performed. P value of <0.05 was considered significant. The MMP-9 expression in CRC was significantly higher compared to adenomas or the normal mucosa (P = 0.001). Significantly higher expression of MMP-9 has been observed in adenomas with high grade dysplasia compared to other adenomas or normal colon (P < 0.001). Diffuse strong MMP-9 expression was present in tumor as well as in stromal cells. In adenoma samples, dysplastic epithelial cells showed moderate intensive cytoplasmic MMP-9 expression, with a clear-cut differentiation between dysplastic and non-dysplastic areas. Staining intensity correlated with the grade of CRC. We demonstrate a significantly higher expression of MMP-9 in adenoma with high grade dysplasia-CRC sequence as compared to normal tissue. The over-expression of MMP-9 strongly suggests its association with colorectal carcinogenesis.
authors.affiliation: 2nd Department of Medicine, Semmelweis University, 1088 Szentkirályi str. 46, Budapest, Hungary. hersz@bel2.sote.hu
authors.forename: László
authors.initials: L
authors.lastname: Herszényi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.forename: Orsolya
authors.initials: O
authors.lastname: Galamb
authors.forename: Norbert
authors.initials: N
authors.lastname: Solymosi
authors.forename: István
authors.initials: I
authors.lastname: Hritz
authors.forename: Pál
authors.initials: P
authors.lastname: Miheller
authors.forename: Lajos
authors.initials: L
authors.lastname: Berczi
authors.forename: Béla
authors.initials: B
authors.lastname: Molnár
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000704:Analysis of Variance; D003106:Colon / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D020780:Matrix Metalloproteinase 9