BACKGROUND Non‐Hodgkin lymphoma (NHL) represents a heterogeneous group of tumors that vary with regard to their biologic aggressiveness and clinical course. In in vitro studies, matrix metalloproteinase 9 (MMP9) was reportedly expressed by human NHL cells and elevated levels of MMP9 have been observed in a subset of patients with high‐grade NHL. METHODS The expression of MMP2 and MMP9 was evaluated in 158 patients with NHL and the relation between the expression of these proteins and clinicopathologic factors was analyzed. All but 1 patient had received radiation therapy and 92 patients also were treated with intensive combination chemotherapy. RESULTS Nearly all the patients with extranodal natural killer NK/T‐cell lymphoma nasal type and anaplastic large cell lymphoma, T‐cell/null cell type expressed MMP9. In contrast, only a small fraction of the patients with mucosa‐associated lymphoid tissue (MALT) lymphomas and follicular lymphomas expressed MMP9. Approximately 50% of the diffuse large B‐cell lymphoma (DLBCL) cases expressed MMP9. The expression of MMP2 was noted in some of the patients with DLBCL and nasal NK/T‐cell lymphoma. The overall survival rates of patients who expressed MMP9 were significantly lower than that of those who did not. Such a correlation was not demonstrated in MMP2 expression. When MMP9 expression was analyzed in DLBLC patients, the overall survival rates of patients who expressed MMP9 were significantly lower than those who did not express MMP9. Chemotherapy was associated with better overall survival in DLBCL patients who expressed MMP9. Overall survival rates of T‐cell/NK‐cell lymphoma patients who expressed MMP9 appeared to be lower than that in those who did not express MMP9. However, chemotherapy was not found to improve overall survival in patients who expressed MMP9. CONCLUSIONS MMP9 expression was observed in patients with aggressive NHL and was characterized by poor overall survival. Cancer 2004;100:356–65.© 2003 American Cancer Society.

The DNA double-strand breaks (DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role with DNA DSBs repair. In this study, 93 of untreated cancer patients and 41 of cancer-free healthy volunteers were enrolled. Peripheral blood was collected, separated and centrifuged; DNA-PK activity was measured by DNA-pull-down assay. The expressions of DNA-PKcs, Ku70 and Ku86 were examined by RT-PCR assay and western blotting. Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activities of peripheral blood lymphocytes (PBL) in patients with uterine cervix or breast cancer were significantly lower than those in normal volunteers. Age and smoking had no association with DNA-PK activity, whereas DNA-PK activity and the expression of Ku70, Ku86 and DNA-PKcs in RT-PCR were interrelated. A similar tendency was seen in western blot assay but less clear than in RT-PCR. Therefore, the association between DNA-PK activity and expression of DNA-PK in protein level could not be concluded. The frequency of chromosome aberration, such as dicentric chromosomes and excess fragment increased as the DNA-PK activity decreased. In conclusion, DNA-PK activity is associated with chromosomal instability. DNA-PK activity in PBL is associated with risk of breast and uterine cervix cancer. DNA-PK activity in PBL can be used to select individuals for whom an examination should be performed because of their increased susceptibility to breast and uterine cervix cancer.

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