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Kazuma Kiyotani - One of the best experts on this subject based on the ideXlab platform.
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Diagnostic utility of STAT6^YE361 expression in Classical Hodgkin Lymphoma and related entities
Modern Pathology, 2020Co-Authors: Charles Slambrouck, Joo Y. Song, Madhu P. Menon, Jooryung Huh, Cheolwon Suh, Aliyah R. Sohani, Amy S. Duffield, Reva C. Goldberg, Paola Dama, Kazuma KiyotaniAbstract:Although the distinction of Classical Hodgkin Lymphoma from nodular lymphocyte predominant Hodgkin Lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin Lymphoma and diagnostically challenging B- and T-cell non-Hodgkin Lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 Classical Hodgkin Lymphomas (31% EBV+), 34 nodular lymphocyte predominant Hodgkin Lymphomas, 34 mimicking B- and T-cell non-Hodgkin Lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6^YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 ( PD-L1 ) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6^YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most Classical Hodgkin Lymphomas showed nuclear staining for STAT6^YE361 [46/57 cases (80%)] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26%)], while dual nuclear and cytoplasmic localization was more common [34/46 (74%)]. In contrast, all nodular lymphocyte predominant Hodgkin Lymphomas [0/34 (0%)] were negative for nuclear STAT6^YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin Lymphomas, nuclear STAT6^YE361 was seen in: B-cell Lymphoma unclassifiable with features intermediate between diffuse large B-cell Lymphoma and Classical Hodgkin Lymphoma, and in primary mediastinal large B-cell Lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell Lymphoma unclassifiable with features intermediate between diffuse large B-cell Lymphoma and Classical Hodgkin Lymphoma, although STAT6^YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one Classical Hodgkin Lymphoma patient positive for nuclear STAT6^YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6^YE361 nuclear staining has 100% positive predictive value and 85.7% negative predictive value in confirming or excluding Classical Hodgkin Lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin Lymphoma and other benign and malignant entities.
Daniel M Knowles - One of the best experts on this subject based on the ideXlab platform.
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expression of cancer testis antigen ct45 in Classical Hodgkin Lymphoma and other b cell Lymphomas
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M KnowlesAbstract:Abstract We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in various epithelial cancers at a frequency of <5% to ∼35%. In this study, the protein expression of CT45 was examined in non-Hodgkin B-cell Lymphomas and Classical Hodgkin Lymphoma by immunohistochemical analysis. Serological response to CT45 was also evaluated by ELISA using CT45 recombinant protein and sera from patients with Hodgkin Lymphoma. None of the 80 low-grade B-cell Lymphomas, including chronic lymphocytic leukemia/small lymphocytic Lymphoma, follicular Lymphoma, and mantle cell Lymphoma, expressed CT45. In comparison, CT45 was expressed in 28 of 126 (22%) diffuse large B-cell Lymphomas (DLBCL). A remarkably high percentage (42/72, 58%) of Classical Hodgkin Lymphoma contained CT45-positive Reed–Sternberg cells. Nodular sclerosis and mixed-cellularity subtypes had similar frequency of CT45 expression, but most EBV-positive cases were CT45 negative. Gray-zone Lymphoma (cases with features of both DLBCL and Classical Hodgkin Lymphoma) also showed frequent (64%) CT45 expression. Evaluation of reactive lymphoid tissues showed scattered CT45-positive lymphocytes in a single case of florid follicular hyperplasia, raising the possibility that this case was an evolving malignancy. Despite frequent CT45 expression, only 1 of 67 Hodgkin Lymphoma patients had detectable anti-CT45 antibodies in the serum, suggesting that the immune response to CT45 may be suppressed. In conclusion, Classical Hodgkin Lymphoma has the highest frequency of CT45 expression among all malignancies tested to date, the frequency of CT45 expression in DLBCL is similar to that seen in epithelial cancers, and low-grade non-Hodgkin B-cell Lymphomas do not express CT45.
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expression of cancer testis antigen ct45 in Classical Hodgkin Lymphoma and other b cell Lymphomas
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M Knowles, Peishan Lee, Melinda Hsu, Lloyd J OldAbstract:We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in various epithelial cancers at a frequency of <5% to approximately 35%. In this study, the protein expression of CT45 was examined in non-Hodgkin B-cell Lymphomas and Classical Hodgkin Lymphoma by immunohistochemical analysis. Serological response to CT45 was also evaluated by ELISA using CT45 recombinant protein and sera from patients with Hodgkin Lymphoma. None of the 80 low-grade B-cell Lymphomas, including chronic lymphocytic leukemia/small lymphocytic Lymphoma, follicular Lymphoma, and mantle cell Lymphoma, expressed CT45. In comparison, CT45 was expressed in 28 of 126 (22%) diffuse large B-cell Lymphomas (DLBCL). A remarkably high percentage (42/72, 58%) of Classical Hodgkin Lymphoma contained CT45-positive Reed-Sternberg cells. Nodular sclerosis and mixed-cellularity subtypes had similar frequency of CT45 expression, but most EBV-positive cases were CT45 negative. Gray-zone Lymphoma (cases with features of both DLBCL and Classical Hodgkin Lymphoma) also showed frequent (64%) CT45 expression. Evaluation of reactive lymphoid tissues showed scattered CT45-positive lymphocytes in a single case of florid follicular hyperplasia, raising the possibility that this case was an evolving malignancy. Despite frequent CT45 expression, only 1 of 67 Hodgkin Lymphoma patients had detectable anti-CT45 antibodies in the serum, suggesting that the immune response to CT45 may be suppressed. In conclusion, Classical Hodgkin Lymphoma has the highest frequency of CT45 expression among all malignancies tested to date, the frequency of CT45 expression in DLBCL is similar to that seen in epithelial cancers, and low-grade non-Hodgkin B-cell Lymphomas do not express CT45.
Yaotseng Chen - One of the best experts on this subject based on the ideXlab platform.
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expression of cancer testis antigen ct45 in Classical Hodgkin Lymphoma and other b cell Lymphomas
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M KnowlesAbstract:Abstract We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in various epithelial cancers at a frequency of <5% to ∼35%. In this study, the protein expression of CT45 was examined in non-Hodgkin B-cell Lymphomas and Classical Hodgkin Lymphoma by immunohistochemical analysis. Serological response to CT45 was also evaluated by ELISA using CT45 recombinant protein and sera from patients with Hodgkin Lymphoma. None of the 80 low-grade B-cell Lymphomas, including chronic lymphocytic leukemia/small lymphocytic Lymphoma, follicular Lymphoma, and mantle cell Lymphoma, expressed CT45. In comparison, CT45 was expressed in 28 of 126 (22%) diffuse large B-cell Lymphomas (DLBCL). A remarkably high percentage (42/72, 58%) of Classical Hodgkin Lymphoma contained CT45-positive Reed–Sternberg cells. Nodular sclerosis and mixed-cellularity subtypes had similar frequency of CT45 expression, but most EBV-positive cases were CT45 negative. Gray-zone Lymphoma (cases with features of both DLBCL and Classical Hodgkin Lymphoma) also showed frequent (64%) CT45 expression. Evaluation of reactive lymphoid tissues showed scattered CT45-positive lymphocytes in a single case of florid follicular hyperplasia, raising the possibility that this case was an evolving malignancy. Despite frequent CT45 expression, only 1 of 67 Hodgkin Lymphoma patients had detectable anti-CT45 antibodies in the serum, suggesting that the immune response to CT45 may be suppressed. In conclusion, Classical Hodgkin Lymphoma has the highest frequency of CT45 expression among all malignancies tested to date, the frequency of CT45 expression in DLBCL is similar to that seen in epithelial cancers, and low-grade non-Hodgkin B-cell Lymphomas do not express CT45.
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expression of cancer testis antigen ct45 in Classical Hodgkin Lymphoma and other b cell Lymphomas
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M Knowles, Peishan Lee, Melinda Hsu, Lloyd J OldAbstract:We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in various epithelial cancers at a frequency of <5% to approximately 35%. In this study, the protein expression of CT45 was examined in non-Hodgkin B-cell Lymphomas and Classical Hodgkin Lymphoma by immunohistochemical analysis. Serological response to CT45 was also evaluated by ELISA using CT45 recombinant protein and sera from patients with Hodgkin Lymphoma. None of the 80 low-grade B-cell Lymphomas, including chronic lymphocytic leukemia/small lymphocytic Lymphoma, follicular Lymphoma, and mantle cell Lymphoma, expressed CT45. In comparison, CT45 was expressed in 28 of 126 (22%) diffuse large B-cell Lymphomas (DLBCL). A remarkably high percentage (42/72, 58%) of Classical Hodgkin Lymphoma contained CT45-positive Reed-Sternberg cells. Nodular sclerosis and mixed-cellularity subtypes had similar frequency of CT45 expression, but most EBV-positive cases were CT45 negative. Gray-zone Lymphoma (cases with features of both DLBCL and Classical Hodgkin Lymphoma) also showed frequent (64%) CT45 expression. Evaluation of reactive lymphoid tissues showed scattered CT45-positive lymphocytes in a single case of florid follicular hyperplasia, raising the possibility that this case was an evolving malignancy. Despite frequent CT45 expression, only 1 of 67 Hodgkin Lymphoma patients had detectable anti-CT45 antibodies in the serum, suggesting that the immune response to CT45 may be suppressed. In conclusion, Classical Hodgkin Lymphoma has the highest frequency of CT45 expression among all malignancies tested to date, the frequency of CT45 expression in DLBCL is similar to that seen in epithelial cancers, and low-grade non-Hodgkin B-cell Lymphomas do not express CT45.
Anke Van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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prognostic model to predict post autologous stem cell transplantation outcomes in Classical Hodgkin Lymphoma
Journal of Clinical Oncology, 2017Co-Authors: Fong Chun Chan, Arjan Diepstra, Anke Van Den Berg, Peter Kamper, Anja Mottok, Alina S Gerrie, Maryse M Power, Marcel Nijland, Francesco Damore, Alexander Lindholm DamoreAbstract:PurposeOur aim was to capture the biology of Classical Hodgkin Lymphoma (cHL) at the time of relapse and discover novel and robust biomarkers that predict outcomes after autologous stem-cell transplantation (ASCT).Materials and MethodsWe performed digital gene expression profiling on a cohort of 245 formalin-fixed, paraffin-embedded tumor specimens from 174 patients with cHL, including 71 with biopsies taken at both primary diagnosis and relapse, to investigate temporal gene expression differences and associations with post-ASCT outcomes. Relapse biopsies from a training cohort of 65 patients were used to build a gene expression–based prognostic model of post-ASCT outcomes (RHL30), and two independent cohorts were used for validation.ResultsGene expression profiling revealed that 24% of patients exhibited poorly correlated expression patterns between their biopsies taken at initial diagnosis and relapse, indicating biologic divergence. Comparative analysis of the prognostic power of gene expression measur...
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the microenvironment in Classical Hodgkin Lymphoma an actively shaped and essential tumor component
Seminars in Cancer Biology, 2014Co-Authors: Yuxuan Liu, Arjan Diepstra, Lydia Visser, Ahmad Sattarzadeh, Anke Van Den BergAbstract:Classical Hodgkin Lymphoma (cHL) is characterized by a minority of tumor cells derived from germinal center B-cells and a vast majority of non-malignant reactive cells. The tumor cells show a loss of B-cell phenotype including lack of the B-cell receptor, which makes the tumor cells vulnerable to apoptosis. To overcome this threat, tumor cells and their precursors depend on anti-apoptotic and growth stimulating factors that are obtained via triggering of multiple membrane receptors. In addition, tumor cells shape the environment by producing a wide variety of chemokines and cytokines. These factors alter the composition of the microenvironment and modulate the nature and effectiveness of the infiltrating cells. The attracted cells enhance the pro-survival and growth stimulating signals for the tumor cells. To escape from an effective anti-tumor response tumor cells avoid recognition by T and NK cells, by downregulation of HLA molecules and modulating NK and T-cell receptors. In addition, the tumor cells produce immune suppressive cytokines that inhibit cytotoxic responses. In this review the relevance of the microenvironment in the pathogenesis of cHL will be discussed.
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Expression of CD1d and presence of invariant NKT cells in Classical Hodgkin Lymphoma
American Journal of Hematology, 2010Co-Authors: Riemer De Vries, Arjan Diepstra, Sibrand Poppema, Lydia Visser, Stephan D Gadola, Anke Van Den BergAbstract:We studied CD1d-restricted invariant natural killer T (iNKT) cells in Classical Hodgkin Lymphoma (cHL). Tumor cells stained positive for CD1d in 21/44 cHL cases, whereas in non-Hodgkin Lymphoma (NHL) only 9/31 stained positive. In contrast, CD1c expression was more common in NHL. The percentage of iNKT cells in cHL cell suspensions was similar to the percentage in reactive lymph nodes and was not related to the CD1d expression status of the tumor cells. In conclusion, we found expression of CD1d in HRS cells in half of the cHL cases, and also observed a substantial population of iNKT cells in cHL cell suspensions.
Charles Slambrouck - One of the best experts on this subject based on the ideXlab platform.
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Diagnostic utility of STAT6^YE361 expression in Classical Hodgkin Lymphoma and related entities
Modern Pathology, 2020Co-Authors: Charles Slambrouck, Joo Y. Song, Madhu P. Menon, Jooryung Huh, Cheolwon Suh, Aliyah R. Sohani, Amy S. Duffield, Reva C. Goldberg, Paola Dama, Kazuma KiyotaniAbstract:Although the distinction of Classical Hodgkin Lymphoma from nodular lymphocyte predominant Hodgkin Lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin Lymphoma and diagnostically challenging B- and T-cell non-Hodgkin Lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 Classical Hodgkin Lymphomas (31% EBV+), 34 nodular lymphocyte predominant Hodgkin Lymphomas, 34 mimicking B- and T-cell non-Hodgkin Lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6^YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 ( PD-L1 ) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6^YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most Classical Hodgkin Lymphomas showed nuclear staining for STAT6^YE361 [46/57 cases (80%)] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26%)], while dual nuclear and cytoplasmic localization was more common [34/46 (74%)]. In contrast, all nodular lymphocyte predominant Hodgkin Lymphomas [0/34 (0%)] were negative for nuclear STAT6^YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin Lymphomas, nuclear STAT6^YE361 was seen in: B-cell Lymphoma unclassifiable with features intermediate between diffuse large B-cell Lymphoma and Classical Hodgkin Lymphoma, and in primary mediastinal large B-cell Lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell Lymphoma unclassifiable with features intermediate between diffuse large B-cell Lymphoma and Classical Hodgkin Lymphoma, although STAT6^YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one Classical Hodgkin Lymphoma patient positive for nuclear STAT6^YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6^YE361 nuclear staining has 100% positive predictive value and 85.7% negative predictive value in confirming or excluding Classical Hodgkin Lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin Lymphoma and other benign and malignant entities.