Clinicopathologic implication of PD-L1 gene alteration in primary adrenal diffuse large B cell lymphoma
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Background: Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications. Methods: We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90). Results: PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012). Conclusions: PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.
Abstract
Background: Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications. Methods: We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90). Results: PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012). Conclusions: PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.
참고문헌 (22)
- Swerdlow SH, "The 2016 revision of the World Health Organization classification of lymphoid neoplasms", Blood, 127, pp.2375~2390 (2016)
- Nagasaki J, "The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma", Blood Adv, 4, pp.4069~4082 (2020)
- Xu-Monette ZY, "PD-1 expression and clinical PD-1 blockade in B-cell lymphomas", Blood, 131, pp.68~83 (2018)
- Roemer MG, "PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome", J Clin Oncol, 34, pp.2690~2697 (2016)
- Ansell SM, "PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma", N Engl J Med, 372, pp.311~319 (2015)
- Kwon HJ, "Clinicopathologic implication of PD-L1 and phosphorylated STAT3 expression in diffuse large B cell lymphoma", J Transl Med, 16, pp.320~ (2018)
- Twa DD, "Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma", Blood, 123, pp.2062~2065 (2014)
- Chapuy B, "Targetable genetic features of primary testicular and primary central nervous system lymphomas", Blood, 127, pp.869~881 (2016)
- Cohen R, "Adrenal gland as a sanctuary site for immunotherapy in patients with microsatellite instability-high metastatic colorectal cancer", J Immunother Cancer, 9, pp.e001903~ (2021)
- Mushtaq RR, "Adrenal metastases in malignant melanoma, is it a privileged site?", J Clin Oncol, 37(15 Suppl), pp.e21016~ (2019)
- Rashidi A, "Primary adrenal lymphoma : a systematic review", Ann Hematol, 92, pp.1583~1593 (2013)
- Kim YR, "Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximabCHOP chemotherapy from the Consortium for Improving Survival of Lymphoma(CISL)", J Hematol Oncol, 5, pp.49~ (2012)
- Laurent C, "Adrenal lymphoma : presentation, management and prognosis", QJM, 110, pp.103~109 (2017)
- Mozos A, "Most primary adrenal lymphomas are diffuse large B-cell lymphomas with non-germinal center B-cell phenotype, BCL6 gene rearrangement and poor prognosis", Mod Pathol, 22, pp.1210~1217 (2009)
- Audrito V, "PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR17-5p", Oncotarget, 8, pp.15894~15911 (2017)
- Gao Q, "Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma", Clin Cancer Res, 15, pp.971~979 (2009)
- Hans CP, "Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray", Blood, 103, pp.275~282 (2004)
- Bardhan K, "The PD1 : PD-L1", 2 pathway from discovery to clinical implementation, 2016, pp.7, 550~
- Hudson K, "The extrinsic and intrinsic roles of PD-L1 and its receptor PD-1 : implications for immunotherapy treatment", Front Immunol, 11, pp.568931~ (2020)
- Pasqualucci L, "The genetic landscape of diffuse large B-cell lymphoma", Semin Hematol, 52, pp.67~76 (2015)
- Iqbal J, "Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma", Leukemia, 21, pp.2332~2343 (2007)
- Peng C, "BCL6-mediated silencing of PD-1 ligands in germinal center B cells maintains follicular T cell population", J Immunol, 202, pp.704~713 (2019)