Journal of Pathology and Translational Medicine

Original Articles

Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation: Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon; J Pathol Transl Med. 2016;50(5):369-376. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.06

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Background
A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs).
Methods
The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs.
Results
The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression.
Conclusions
HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.

Citations

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Long noncoding RNAs (lncRNAs) in HIV-mediated carcinogenesis: Role in cell homeostasis, cell survival processes and drug resistance
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Non-coding RNA Research.2022; 7(3): 184. CrossRef
Biomedical impact of the expression of HOX locus-associated LncRNAs HOTAIR and HOTTIP in diffuse large B cell lymphoma
Mona Salah Eldin Habieb, Suzy Fawzy Goher, Abd-Elmonem Abd-Elkader El-Torgman, Ibrahim El Tantawy El Sayed, Najlaa Zanati Ali Abd-Elfattah
Human Gene.2022; 34: 201112. CrossRef
Mechanism of LncHOTAIR Regulating Proliferation, Apoptosis, and Autophagy of Lymphoma Cells through hsa-miR-6511b-5p/ATG7 Axis
Fu Gui, Xinyi Yu, Yemeng Wu, Chao Wu, Yulan Zhang, Peng-Yue Zhang
Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1. CrossRef
Circulating RNA biomarkers in diffuse large B-cell lymphoma: a systematic review
Philippe Decruyenaere, Fritz Offner, Jo Vandesompele
Experimental Hematology & Oncology.2021;[Epub] CrossRef
Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness
Mahmoud A. Senousy, Aya M. El-Abd, Raafat R. Abdel-Malek, Sherine M. Rizk
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CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas.: Kyueng Whan Min, Young Ha Oh, Chan Kum Park, So Dug Lim, Wan Seop Kim; Korean J Pathol. 2011;45(6):589-595.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.589

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Abstract PDF: BACKGROUND
CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms.
METHODS
Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated.
RESULTS
A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041).
CONCLUSIONS
High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.

Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.: Young Sin Ko, Young Ha Oh, Chan Kum Park, Wook Youn Kim, Hye Seung Han, So Dug Lim, Tae Sook Hwang, Wan Seop Kim; Korean J Pathol. 2011;45(6):573-581.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.573

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Abstract PDF

BACKGROUND
Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity.
METHODS
We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x).
RESULTS
Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score.
CONCLUSIONS
The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.

Citations

Citations to this article as recorded by

Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies
Pauline Gravelle, Barbara Burroni, Sarah Péricart, Cédric Rossi, Christine Bezombes, Marie Tosolini, Diane Damotte, Pierre Brousset, Jean-Jacques Fournié, Camille Laurent
Oncotarget.2017; 8(27): 44960. CrossRef
Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis
Wook Youn Kim, Ho Young Jung, Soo Jeong Nam, Tae Min Kim, Dae Seog Heo, Chul-Woo Kim, Yoon Kyung Jeon
Virchows Archiv.2016; 469(5): 581. CrossRef

Case Report

Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation Manifested as a Soft Tissue Mass: Incidental Discovery on Histological Examination.: Sang Yun Ha, Yoon La Choi, Sung Joo Kim, Young Hye Ko; Korean J Pathol. 2011;45(4):417-422.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.417

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Abstract PDF

We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.

Citations

Citations to this article as recorded by

EBV-negative Fibrin-Associated Large B-Cell Lymphoma Arising in Thyroid Hyperplastic Nodule: Report of a Case and Literature Review
Tin Wai Ho, Wah Cheuk, John K.C. Chan
International Journal of Surgical Pathology.2023; 31(7): 1420. CrossRef
Diffuse Large B Cell Lymphoma in a Prosthetic Aortic Graft
David Bell, David Marshman
Heart, Lung and Circulation.2017; 26(2): e4. CrossRef
Fibrin-associated EBV-positive Large B-Cell Lymphoma
Daniel F. Boyer, Penelope A. McKelvie, Laurence de Leval, Kerstin L. Edlefsen, Young-Hyeh Ko, Zachary A. Aberman, Alexandra E. Kovach, Aneal Masih, Ha T. Nishino, Lawrence M. Weiss, Alan K. Meeker, Valentina Nardi, Maryknoll Palisoc, Lina Shao, Stefania P
American Journal of Surgical Pathology.2017; 41(3): 299. CrossRef
Malignant Lymphoma Mimicking an Infection After Shoulder Surgery
Jabari Ian Justin Martin, Jasmine Bauknight, Vincent Desiderio, Bahman Sadr
Journal of the American Academy of Orthopaedic Surgeons.2017; 25(4): 314. CrossRef
Current Concepts in Primary Effusion Lymphoma and Other Effusion-Based Lymphomas
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Korean Journal of Pathology.2014; 48(2): 81. CrossRef

Original Articles

Association of CD57+ Natural Killer Cells with Better Overall Survival in DLBCL Patients.: Jeong Hyeon Lee, Yoon Jin Kwak, Chul Hwan Kim, Insun Kim; Korean J Pathol. 2011;45(4):361-370.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.361

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Abstract PDF

BACKGROUND
Malignant tumor cells may evoke the innate and adaptive immune systems. Various immune cells are involved in this immune reaction, and tumor infiltrating lymphocytes, macrophages, natural killer (NK) cells are associated with patient prognosis for solid tumors.
METHODS
Seventy-eight patients who were diagnosed with diffuse large B cell lymphoma (DLBCL) between 2001 and 2009 were selected. CD57+ NK cells, CD68+ tumor associated macrophages (TAMs), and CD4+ and CD8+ T cells were evaluated in tissue sections using immunohistochemical staining and compared with clinical parameters including age, gender, performance status, clinical stage, serum lactic dehydrogenase level, number of extranodal sites, international prognostic index score, chemotherapy response, and survival.
RESULTS
Patients with high numbers of CD57+ NK cells had a significantly higher overall survival rate than patients with low numbers of CD57+ NK cells. However, no significant difference was observed between the number of CD57+ NK cells and other prognostic parameters. The number of CD68+ TAMs and CD4+ or CD8+ T cells was not significantly correlated with prognostic factors in patients with DLBCL.
CONCLUSIONS
An evaluation of tumor infiltrating CD57+ NK cells is recommended as a prognostic indicator in patients with DLBCL.

Citations

Citations to this article as recorded by

The prognostic value of tumor-associated macrophages detected by immunostaining in diffuse large B cell lymphoma: A meta-analysis
Mei Lin, Shupei Ma, Lingling Sun, Zhiqiang Qin
Frontiers in Oncology.2023;[Epub] CrossRef

Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.: Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon; Korean J Pathol. 2009;43(4):317-320.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.

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