Chunmei Li

Nagoya City University, Nagoya, Aichi, Japan

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Publications (9)36.03 Total impact

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    ABSTRACT: Abstract Although rare, thymic mucosa-associated lymphoid tissue (MALT) lymphoma is considered to be a distinct clinicopathological entity. Using a methylation-specific polymerase chain reaction, we analyzed thymic MALT lymphomas (n=18) for their methylation of the following seven tumor suppressor genes: DAPK1, p16(INK4A), p14(ARF), CDH1, RARB, TIMP3, and MGMT. Reactive lymph nodes (n=16) were used as a control. Of the seven genes examined, thymic MALT lymphomas had an increased number of genes that were methylated (2.9 genes) as compared with reactive lymph nodes (0.63, p=0.0003). In particular, thymic MALT lymphomas showed a frequent methylation of DAPK1, CDH1, TIMP3, and p14(ARF). In addition, gene methylation of the p14(ARF) was associated with a larger tumor size while that of the other three genes was not associated with any clinicopathological features examined. This study suggests that methylation of tumor suppressor genes may play an important role in thymic MALT lymphoma.
    Leukemia & lymphoma 01/2013; · 2.61 Impact Factor
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    ABSTRACT: Primary cutaneous marginal zone B-cell lymphoma is considered the cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Although its molecular pathogenesis is currently unknown, an etiological link with Borrelia burgdorferi infection has been identified in European, but not in American or Asian cases. To better understand the pathogenesis and the geographical differences of cutaneous marginal zone B-cell lymphoma, 60 cases from the East Asia, Germany, and the United States at their initial presentation were subjected to the following analyses; (1) clinicopathological comparison between the geographical regions, (2) detection of B. burgdorferi DNA, (3) detection of the API2-MALT1 fusion transcript, a gene alteration specific to mucosa-associated lymphoid tissue lymphoma, and (4) inactivation of tumor suppressor genes (death-associated protein kinase (DAPK), p16(INK4a), p14(ARF), MGMT, TIMP3, CDH1, and RARB) by hypermethylation of the CpG islands. Cases from the three geographical regions showed similar clinicopathological features. However, moderate/marked tissue eosinophilia was found in 9/25 Asian cases, but only 1/23 German cases (P=0.011) and 0/12 American cases (P=0.015). All 60 cases were negative for either Borrelia DNA or API2-MALT1 fusion. Tumors from the three regions were highly methylated for DAPK (38-50% of the cases, mean 43%) and p16(INK4a) (42-70%, mean 49%), and the positivities were significantly higher than those of nonneoplastic skin (8%, P=0.0010 and 14%, P=0.0032, respectively). Methylation of these genes had no significant association with progressive features of the tumor. Primary cutaneous marginal zone B-cell lymphomas from the three geographical regions have common clinicopathological features, however, moderate/marked tissue eosinophilia is a feature found almost exclusively in Asian cases. Borrelia infection and API2-MALT1 fusion are not significant in this tumor. Methylation of DAPK and p16(INK4a) genes is a frequent event in this lymphoma at its initial presentation, but may not be associated with tumor progression.
    Modern Pathology 10/2008; 21(12):1517-26. · 5.25 Impact Factor
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    ABSTRACT: Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare, and only five cases have been reported. Reported herein is a new case that has involved a 9 year follow up. A 79-year-old man was treated with transurethral resection (TUR) for a mass of the right prostatic lobe, and followed up under a diagnosis of benign prostatic hyperplasia with atypical lymphoid infiltration. Seven years later TUR was again performed for a right lobe mass. The lesion was diagnosed as a relapsed MALT lymphoma after detailed histological and immunoglobulin heavy chain gene analyses of the initial and relapsed lesions. Interestingly, lymphoepithelial lesions were observed only infrequently in this tumor. The API2-MALT1 fusion, a gene alteration specific to MALT lymphoma, was absent. The patient had stage IA disease at the time of tumor relapse, and has been alive and well for the 2 years after the second TUR. The present case suggests that despite tumor recurrence, prostatic MALT lymphoma is indolent, and function-preserving therapy is warranted.
    Pathology International 04/2008; 58(3):191-5. · 1.72 Impact Factor
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    ABSTRACT: In anaplastic large-cell lymphomas positive for anaplastic lymphoma kinase (ALK) protein, the ALK gene is most commonly fused to the NPM gene, and less commonly to TPM3, TFG, ATIC, and other rare genes. Although this lymphoma is generally associated with a favorable clinical outcome, 25% of the patients die of the disease within 5 years. In this study, we developed three assays, all of which can be used with archival formalin-fixed, paraffin-embedded tissues: (1) a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay for various X-ALK fusion genes, (2) a 5' rapid amplification of cDNA ends (RACE) assay to identify unknown fusion partners, and (3) a real-time RT-PCR assay to quantify the amount of the NPM-ALK fusion transcript. In 26 cases of ALK(+) anaplastic large-cell lymphoma, the RT-PCR assay showed that the ALK was fused to NPM in 21 cases, to TPM3 in three, and to TFG in one. The 5' RACE assay detected ATIC-ALK fusion in the remaining case. The real-time quantitative RT-PCR assay showed that the NPM-ALK transcript was over expressed in four of 20 quantifiable cases. Patients with NPM-ALK overexpression showed a significantly unfavorable overall survival compared with those with a low expression of this transcript. The RT-PCR and 5' RACE assays developed here may be useful for identification of known and unknown gene partners fused to the ALK gene. Overexpression of the NPM-ALK fusion transcript may be associated with a poor prognosis of the patients with ALK(+) anaplastic large-cell lymphomas.
    Modern Pathology 07/2007; 20(6):648-55. · 5.25 Impact Factor
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    ABSTRACT: p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2-MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2-MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42%) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60%) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55%). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2-MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.
    Modern Pathology 10/2005; 18(9):1187-92. · 5.25 Impact Factor
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    ABSTRACT: Mucosa-associated lymphoid tissue (MALT) lymphoma constitutes up to 90% of primary pulmonary lymphomas, but its diagnosis is often difficult. API2-MALT1 fusion is specific to MALT lymphoma and is detected in nearly half of the pulmonary cases. Cytologic examinations have played a pivotal role in the diagnosis of pulmonary tumors; however, cytologic specimens have only infrequently been used for molecular studies. In this study, we performed a multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the API2-MALT1 fusion transcript in archival cytologic specimens used as RNA sources. We studied 3 pulmonary MALT lymphoma cases that were positive for the fusion gene as detected with RNA extracted from diagnostic histologic specimens. In 1 case, a conventional PCR clonality assay for the immunoglobulin heavy chain gene rearrangement failed to detect the monoclonality. In all 3 cases, the fusion transcript was successfully detected in the cytologic specimens of sputum, bronchoalveolar lavage fluid, bone marrow smears, and pleural effusions. This finding suggests that such specimens can be used as RNA sources in multiplex RT-PCR assays for the API2-MALT1 fusion transcript. The detection of API2-MALT1 fusion as carried out with these specimens would be useful as an ancillary assay for the diagnosis, staging, and follow-up of pulmonary MALT lymphoma.
    International Journal of Hematology 08/2005; 82(1):59-62. · 1.68 Impact Factor
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    ABSTRACT: Gastric MALT lymphoma shows unique features including regression by Helicobacter pylori eradication and API2-MALT1 fusion. We performed a molecular and clinicopathologic study for 115 cases. All eradication-responsive cases were devoid of API2-MALT1 fusion. All tumors positive for the fusion and all negative for H. pylori infection were nonresponsive to the eradication. Consequently, gastric MALT lymphomas were divided into three groups: Eradication-responsive and fusion-negative (group A, n = 72), eradication-nonresponsive and fusion-negative (group B, n = 22), and eradication-nonresponsive and fusion-positive (group C, n = 21). Group A tumors were characterized by low clinical stage and superficial gastric wall involvement, and group C tumors by low H. pylori infection rate, advanced clinical stage, and nuclear BCL10 expression. All group C tumors showed exclusively low-grade histology. Group B tumors, which have not been well recognized, frequently showed nodal involvement, deep gastric wall involvement, and advanced clinical stage, and sometimes an increased large cell component. A multivariate discriminant analysis revealed that responsiveness to the eradication could be predicted accurately by negative API2-MALT1 fusion, positive H. pylori infection, low clinical stage, and superficial gastric wall invasion, the former being the most important factor for the prediction. This 3-group categorization may be helpful for a comprehensive understanding of gastric MALT lymphoma.
    American Journal of Surgical Pathology 01/2005; 28(12):1560-7. · 4.87 Impact Factor
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    ABSTRACT: Cutaneous marginal zone B-cell lymphoma is a recently proposed entity and constitutes a cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Borrelia burgdorferi infection has been suggested as a possible causative agent in European cutaneous cases of marginal zone B-cell lymphoma, whereas API2-MALT1 fusion and BCL10 mutation are highly associated with MALT lymphoma. Aberrant nuclear BCL10 expression may be closely correlated with API2-MALT1 fusion in gastric and pulmonary MALT lymphomas. We examined 24 Asian cases of cutaneous marginal zone B-cell lymphoma for B. burgdorferi involvement, API2-MALT1 fusion, BCL10 cellular expression, and BCL10 mutation. Neither Borrelia DNA nor API2-MALT1 fusion transcript was detected. Nuclear BCL10 expression was evident in tumor cells of 11 of 24 cases, although BCL10 mutation was found in one case only. Clinicopathologically, nuclear BCL10 was more frequently expressed in macroscopically nodular lesions than in plaques or papules (p = 0.0031). These data suggest that 1) B. burgdorferi infection may not play an important role in developing cutaneous marginal zone B-cell lymphoma in Asian cases, 2) neither API2-MALT1 fusion nor BCL10 mutation is closely associated with the pathogenesis, 3) aberrant nuclear BCL10 may frequently be expressed in the absence of these genetic abnormalities, and 4) nuclear BCL10 expression may be clinically important because it was observed in locally aggressive tumors.
    American Journal of Surgical Pathology 09/2003; 27(8):1061-9. · 4.87 Impact Factor
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    ABSTRACT: t(11;18)(q21;q21) is associated with mucosa-associated lymphoid tissue (MALT)-type lymphoma and results in API2-MALT1 fusion. However, its clinicopathologic significance remains unclarified. API2-MALT1 fusion is detected most frequently in MALT lymphomas primarily involving the lung. We therefore screened 51 cases of pulmonary MALT lymphoma for API2-MALT1 fusion, and studied its relationship with clinicopathologic factors including the immunohistochemical expression of BCL10, another MALT lymphoma-associated molecule. The API2-MALT1 fusion transcript was detected in 21 of 51 (41%) cases, and was correlated with the absence of any underlying autoimmune disease, and with a normal serum lactate dehydrogenase, a "typical" histology without marked plasmacytic differentiation or an increased number of large cells, and aberrant nuclear BCL10 expression. However, its prognostic impact was not identified in the limited follow-up (6 to 187 months, median 27). These data suggest that the API2-MALT1 fusion may be a causative gene abnormality unrelated to autoimmune disease. In addition, this alteration may define a homogeneous MALT lymphoma subtype that is clinically more indolent and histologically more "typical." Aberrant nuclear BCL10 expression may have a possible role as a tool to screen for this API2-MALT1 fusion. A large-scale study with a long follow-up is necessary to establish the prognostic significance of API2-MALT1 fusion.
    American Journal Of Pathology 05/2003; 162(4):1113-22. · 4.52 Impact Factor