NK and NK‐like T‐cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status

Ko, Young Hyeh; Cho, E-Y; Kim, J.-E.; Lee, S.-S.; Huh, Jooryung; Chang, Heng; Yang, Woo‐Ick; Kim, C.-W.; Kim, S.-W.; Ree, H. J.

doi:10.1111/j.1365-2559.2004.01867.x

Cited by 128 publications

(111 citation statements)

References 11 publications

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“…This disease entity encompasses all NK/T cell lymphomas occurring outside nasal cavity and nasopharynx and is notorious for its aggressive clinical course. The definition of nasal-type is confusing, which resulted in different categorisation by various institutions (Kern et al, 1992;Wong et al, 1992;Peiper, 1993;Nakamura et al, 1995;Jaffe et al, 1996Jaffe et al, , 1999Kobashi et al, 1996;Chan et al, 1997;Bekkenk et al, 2004;Ko et al, 2004). We defined nasal-type lymphoma as lesions primarily involving skin, soft tissues, visceral organs such as liver, spleen, and gastrointestinal tract without any lesions within the nasal cavity and/or upper aerodigestive tract such as oral cavity, tonsil, pharynx, and larynx.…”

Section: Discussionmentioning

confidence: 99%

Nasal-type NK/T cell lymphoma: clinical features and treatment outcome

Lee

Kim

Park³

et al. 2005

Br J Cancer

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Nasal-type NK/T cell lymphoma is an increasingly recognised disease entity of aggressive clinical behaviour. The objective of this study was to investigate clinical features and treatment outcomes in patients with nasal-type NK/T cell lymphoma. From January 1991 to December 2003, 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. One half of patients presented with poor performance status (ECOG X2); 46% of patients were categorised as high intermediate or high-risk group according to IPI; and 46% of patients were diagnosed at advanced stage. The median survival for 26 patients with nasal-type NK/T cell lymphoma was 7.4 months (95% CI, 0.1, 16.9). The treatment outcome of primary anthracycline-based chemotherapy was poor: 60% CR rate in localised disease and 0% CR rate in advanced disease. After a median follow-up of 24.4 months (range 3.1 -99.0) in patients with localised disease who had achieved a CR (range 29.6 -165.7), three patients (50.0%) developed disease recurrence at 6.1, 21.8, and 52.1 months, respectively, and all patients presented with locoregional failure. The predictive factors for poor survival were of age greater than 60, advanced stage and poor performance in multivariate analysis. In conclusion, Nasal-type NK/T cell lymphomas showed a poor response to the conventional anthracycline-based chemotherapy, and thus an investigation for an innovative therapy is urgently needed to improve survival in these patients.

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Section: Discussionmentioning

confidence: 99%

Nasal-type NK/T cell lymphoma: clinical features and treatment outcome

Lee

Kim

Park³

et al. 2005

Br J Cancer

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“…All of the 16 patients had pathologically confirmed NK/T cell lymphoma with positive immunostaining results for cytoplasmic CD3 and CD56 and Epstein-Barr virus (EBV) in situ hybridization. 16,17 To investigate a potential role and the indications of HDC/ASCT in treatment of extranodal NK/T-cell lymphoma, a subset analysis comparing HDC/ASCT recipients and non-recipients was performed in regards to relapse-free survival (RFs) duration and overall survival (OS) duration. The conditioning regimens used for ASCT were BEAM (carmustine, etoposide, cytarabine melphalan) in twelve patients, VCT (VP-16, cyclophosphamide, total body irradiation of 9 Gy) in two patients, VCB (VP-16, cyclophosphamide, busulphan) in one patient and BEAC (carmustine, etoposide, cytarabine, cyclophosphamide) in one patient.…”

Section: Methodsmentioning

confidence: 99%

High-dose chemotherapy with autologous stem cell transplantation in extranodal NK/T-cell lymphoma: a retrospective comparison with non-transplantation cases

Kim

Bang

Lee

et al. 2006

Bone Marrow Transplant

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“…Considering the correlation between the extent of tumor necrosis and worse prognosis of the patients, as shown in the previous study, 26 the EBV-induced cytokine secretion appears to be an important pathogenetic factor that determines the clinicopathologic features of NK/T-cell lymphoma.…”

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confidence: 99%

Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma

Park

Jin

et al. 2007

Laboratory Investigation

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This study aims to investigate the role of granzyme B in the apoptosis of nasal-type NK/T-cell lymphoma. Twenty-four nasal-type NK/T-cell lymphomas were examined by TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end labeling (TUNEL) assay and immunohistochemical staining for active caspase 3, poly(ADP-ribose) polymerase (PARP-1/ p85)/p85, and Bcl-2. In addition, HANK-1 and NKL cell lines were analyzed using Western blot analysis. Immunoprecipitation was performed to identify the binding of granzyme B and intrinsic serpin proteinase inhibitor 9 (PI-9). To localize granzyme B, immunogold labeling and immunofluorescence staining were performed. The expression level of granzyme B in tumor tissue was correlated with the apoptosis rate (P ¼ 0.015), degree of necrosis (P ¼ 0.002), and the levels of active caspase 3 (P ¼ 0.036) and poly ADP-ribose polymerase (PARP)-1/p85 (P ¼ 0.040). The granzyme B-positive HANK-1 cell line showed increased spontaneous cell death compared to the granzyme B-negative NKL cell line. The untreated HANK-1 cells released cytochrome c into the cytosol with cleavage of caspase 3 and PARP-1. Treatment with granzyme B inhibitor and caspase inhibitor decreased the cleavage of PARP-1. By performing immunogold labeling, granzyme B was identified within the cytolytic granules as well as in the cytosol. Confocal microscopy and immunoprecipitation assays confirmed the colocalization of PI-9 and granzyme B, which formed an SDS-resistant complex. These results suggested that granzyme B leakage induces cell death in NK/T-cell lymphomas via both caspase-dependent and -independent mechanisms, and this leads to the extensive necrosis that is commonly seen in NK/T-cell lymphoma.

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NK and NK‐like T‐cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status

Cited by 128 publications

References 11 publications

Nasal-type NK/T cell lymphoma: clinical features and treatment outcome

Nasal-type NK/T cell lymphoma: clinical features and treatment outcome

High-dose chemotherapy with autologous stem cell transplantation in extranodal NK/T-cell lymphoma: a retrospective comparison with non-transplantation cases

Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma

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