title: Matrix metalloproteinase-9 is a prognostic marker to predict survival of patients who underwent surgery due to rectal carcinoma.
abstract: Common prognostic factors do not fully predict clinical outcomes in colorectal cancer, one of the most common malignancies in developed countries. Therefore, biological prognostic markers are under investigation. We investigated the prognostic value of expression of matrix metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-2 and TIMP-3) in rectal carcinoma to predict survival of the patients. Retrospective analysis of clinicopathological findings of 64 patients who underwent rectal resection due to carcinoma and were followed-up from 2 to 96 months (median 48) was performed. Semi-quantitative scoring was used to assess the expression levels of MMP-2, MMP-9, TIMP-2 and TIMP-3 in rectal carcinoma. During the follow-up, 28 patients died. The deceased patients demonstrated significantly higher expression of MMP-9 and lower expression of TIMP-3 in parenchyma of carcinoma and lower expression of TIMP-2 in stroma of carcinoma, compared to survivors. Moreover, the deceased patients were associated with advanced tumor, metastases in lymph nodes and distant metastases. According to univariate analysis longer survival was predicted by lower expression of MMP-9 in parenchymal cells (p = 0.03), tumor size (early tumor) (p = 0.026), absence of metastases in lymph nodes (p = 0.02) or distant metastases (p = 0.04). Multivariate analysis revealed that metastases in lymph nodes, higher expression of MMP-9 in parenchyma, and lower expression of MMP-9 in stromal cells significantly increased mortality. Expression of MMP-9 in rectal carcinoma is a prognostic marker for overall survival. It is important to identify the origin of MMP-9 to predict better overall survival of the patients.
authors.affiliation: Department of Surgery, Academy of Medicine, Lithuanian University of Health Science, Kaunas, Lithuania. s.svagzdys@gmail.com
authors.forename: Saulius
authors.initials: S
authors.lastname: Svagzdys
authors.forename: Vaiva
authors.initials: V
authors.lastname: Lesauskaite
authors.forename: Dalia
authors.initials: D
authors.lastname: Pangonyte
authors.forename: Zilvinas
authors.initials: Z
authors.lastname: Saladzinskas
authors.forename: Algimantas
authors.initials: A
authors.lastname: Tamelis
authors.forename: Dainius
authors.initials: D
authors.lastname: Pavalkis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9