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Daniel M Knowles - One of the best experts on this subject based on the ideXlab platform.

  • 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, 2010
    Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M Knowles
    Abstract:

    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.

  • 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, 2010
    Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M Knowles, Peishan Lee, Melinda Hsu, Lloyd J Old
    Abstract:

    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.

Kazuma Kiyotani - One of the best experts on this subject based on the ideXlab platform.

  • Diagnostic utility of STAT6^YE361 expression in classical Hodgkin Lymphoma and related entities
    Modern Pathology, 2020
    Co-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 Kiyotani
    Abstract:

    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.

Sally L Glase - One of the best experts on this subject based on the ideXlab platform.

  • impact of treatment and insurance on socioeconomic disparities in survival after adolescent and young adult Hodgkin Lymphoma a population based study
    Cancer Epidemiology Biomarkers & Prevention, 2016
    Co-Authors: Theresa H M Keega, Mindy C Deroue, Hele M Parsons, Christina A Clarke, Debbie Goldberg, Christophe R Flowers, Sally L Glase
    Abstract:

    Background: Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin Lymphoma among adolescents and young adults (AYA), but did not consider the influence of combined-modality treatment and health insurance. Methods: Data for 9,353 AYA patients ages 15 to 39 years when diagnosed with Hodgkin Lymphoma during 1988 to 2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of sociodemographic characteristics [race/ethnicity, neighborhood socioeconomic status (SES), and health insurance], initial combined-modality treatment, and subsequent cancers on survival. Results: Over the 24-year study period, we observed improvements in Hodgkin Lymphoma–specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES, and health insurance for a subset of more recently diagnosed patients (2001–2011). In multivariable analyses, Hodgkin Lymphoma–specific survival was worse for Blacks than Whites with early-stage [HR: 1.68; 95% confidence interval (CI): 1.14–2.49] and late-stage disease (HR: 1.68; 95% CI, 1.17–2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI, 1.22–2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI, 1.59–2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse Hodgkin Lymphoma–specific survival (HR: 2.08; 95% CI, 1.52–2.84). Conclusion: Our findings identify several subgroups of Hodgkin Lymphoma patients at higher risk for Hodgkin Lymphoma mortality. Impact: Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities. Cancer Epidemiol Biomarkers Prev; 25(2); 264–73. ©2016 AACR .

Yaotseng Chen - One of the best experts on this subject based on the ideXlab platform.

  • 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, 2010
    Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M Knowles
    Abstract:

    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.

  • 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, 2010
    Co-Authors: Yaotseng Chen, Amy Chadburn, Erika Ritter, April Chiu, Sacha Gnjatic, Michael Pfreundschuh, Daniel M Knowles, Peishan Lee, Melinda Hsu, Lloyd J Old
    Abstract:

    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.

Aliyah R. Sohani - One of the best experts on this subject based on the ideXlab platform.

  • Diagnostic utility of STAT6^YE361 expression in classical Hodgkin Lymphoma and related entities
    Modern Pathology, 2020
    Co-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 Kiyotani
    Abstract:

    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.

  • nodular lymphocyte predominant Hodgkin Lymphoma with atypical t cells a morphologic variant mimicking peripheral t cell Lymphoma
    The American Journal of Surgical Pathology, 2011
    Co-Authors: Aliyah R. Sohani, Elaine S Jaffe, Stefania Pittaluga, Judith A. Ferry, Nancy Lee Harris, Robert P Hasserjian
    Abstract:

    Nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) is a distinct Hodgkin Lymphoma subtype composed of few neoplastic lymphocyte-predominant (LP) cells in a background of reactive small B and T cells. We have seen occasional NLPHL cases that contain background T cells with prominent cytologic at