title: Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma.
abstract: The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that promotes plasmablastic differentiation, and the survival of germinal center B-cells. The expression of TIMP-1 is known to be correlated with a subset of non-Hodgkin lymphoma at the mRNA level, and Epstein-Barr virus infection in vitro. To characterize TIMP-1(+) diffuse large B-cell lymphoma, TIMP-1 expression was investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell lymphoma and compared with prognostic factors, immunophenotypes, and Epstein-Barr virus infection status. TIMP-1 was expressed not only in tumor cells themselves, in 14 of 182 cases (8%), designated as TIMP-1(+) diffuse large B-cell lymphoma, but also in stromal cells like fibroblasts and endothelial cells. In univariate analysis and hierarchical clustering, our findings suggest that TIMP-1 expression may represent a distinct subgroup. In multivariate analysis, TIMP-1(+) diffuse large B-cell lymphoma (n=14) was associated with unfavorable outcomes compared to TIMP-1(-) diffuse large B-cell lymphoma (n=168) (odds ratio=2.5, P=0.049). Together with TIMP-1 expression, age (greater than 60 years), the presence of B-symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV) was correlated with a poor overall survival. However, TIMP-1 expression in diffuse large B-cell lymphoma was not correlated with other prognostic factors including: clinical stage, international prognostic index score, and nongerminal center B-cell phenotype, as well as Epstein-Barr virus infection. Our results suggest that TIMP-1 expression may be an independent negative prognostic factor in patients with diffuse large B-cell lymphoma.
authors.affiliation: Department of Pathology and Biostatistics Interest Group, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: An
authors.forename: Ju-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
chemical_list: D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D015260:Neprilysin; D051560:Proto-Oncogene Proteins c-bcl-6; D019715:Tissue Inhibitor of Metalloproteinase-1; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human