Clinicopathologic implications of tissue inhibitor of metalloproteinase-1- positive diffuse large B-cell lymphoma

Jung Woo Choi, Jung Suk An, Ju Han Lee, Eung Seok Lee, Kwang Hee Kim, Young Sik Kim

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)963-973
    Number of pages11
    JournalModern Pathology
    Volume19
    Issue number7
    DOIs
    Publication statusPublished - 2006 Jul 28

    Keywords

    • Non-Hodgkin lymphoma
    • TIMP-1
    • Tissue microarray

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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