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Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior

  • Anna Gerbe
  • Melissa Alame
  • Olivier Dereure
  • Samia Gonzalez
  • Luc Durand
  • Ariane Tempier
  • Laura De Oliveira
  • Alicia Tourneret
  • Valérie Costes-Martineau
  • Valère Cacheux
  • Vanessa SzablewskiEmail author
Original Article

Abstract

Despite distinct clinical presentation and outcome, systemic, primary cutaneous, and breast implant-associated anaplastic large cell lymphomas (S-, PC-, BI-ALCL) ALK-negative (ALK−) show similar histopathological features including the presence of the “hallmark” cells with horseshoe-shaped nuclei and CD30 protein expression. The purpose was to better characterize these three entities using immunohistochemistry and FISH (Fluorescent in situ hybridization) to identify biomarkers differently expressed and that might be involved in their pathogenesis. Twenty-two S-ALCL ALK−, 13 PC-ALCL, and 2 BI-ALCL were included. Cases were tested for P53, P63, MUM1, MYC, GATA3, p-STAT3, PD1, and PDL1 protein expression and DUP22, TP53, TP63, MYC, and PDL1 chromosomal aberrations. As expected, S-ALCL ALK− patients had adverse outcome compare to PC and BI-ALCL. No difference was observed between the three groups concerning protein expression except for MUM1 that was significantly more frequently expressed in S-ALCL ALK− compared to PC-ALCL. In particular, constitutive activation of the STAT3 pathway and PDL1/PD1 immune-checkpoint expression was present in the three entities. TP53 deletion and PDL1 gene amplification were the commonest cytogenetic alterations and were present in the three entities. None of the studied biological parameters was associated with prognosis. Despite distinct clinical behavior, S-ALCL ALK−, PC-ALCL, and BI-ALCL share similar biological features. Larger series should be investigated with the current approach to determine more precisely the activity and the prognostic value of these biomarkers and pathways in each group.

Keywords

Anaplastic lymphoma Cutaneous Breast implant PDL1 STAT3 

Notes

Author contributions

V S, M A, V C-M, and V C designed the research project. V S, A G, L D, and V C-M evaluated the histological and immunohistochemical findings. V S, M A, A T, L D O, A T, and V C evaluated the cytogenetic findings. V S and A G obtained data and wrote the main part of the manuscript. M A, V C-M, O D, S G, L D, A T, and V C reviewed the draft with critical comments.

Compliance with ethical standards

This study was carried out in agreements with the Declaration of Helsinki and was approved by the Centre des Ressources Biologiques (CRB) of the Centre-Hospitalo-Universitaire (CHU) of Montpellier, France.

Informed consent

Written informed consent for the study was obtained from the patient.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

428_2019_2570_MOESM1_ESM.docx (78 kb)
ESM 1 (DOCX 78 kb)

References

  1. 1.
    Johnson NA, Slack GW, Savage KJ et al (2012) Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol 30:3452–3459 Published Online First: 30 July 2012.  https://doi.org/10.1200/JCO.2011.41.0985 CrossRefGoogle Scholar
  2. 2.
    Zhang W, Wang Z, Luo Y et al (2016) GATA3 expression correlates with poor prognosis and tumor-associated macrophage infiltration in peripheral T cell lymphoma. Oncotarget 7:65284–65294.  https://doi.org/10.18632/oncotarget.11673 Google Scholar
  3. 3.
    Chavan RN, Bridges AG, Knudson RA, Ketterling RP, Comfere N, Wada DA, Torres-Cabala C, DiCaudo DJ, Vasmatzis G, Pittelkow MR, Feldman AL (2014) Somatic rearrangement of the TP63 gene preceding development of mycosis fungoides with aggressive clinical course. Blood Cancer J 4:e253.  https://doi.org/10.1038/bcj.2014.73 CrossRefGoogle Scholar
  4. 4.
    Chatzitolios A, Venizelos I, Tripsiannis G, Anastassopoulos G, Papadopoulos N (2010) Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkin’s lymphoma. Ann Hematol 89:889–896.  https://doi.org/10.1007/s00277-010-0945-x CrossRefGoogle Scholar
  5. 5.
    Shukuya T, Carbone DP (2016) Predictive markers for the efficacy of anti-PD-1/PD-L1 antibodies in lung cancer. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 11:976–988. Published Online First: 1 March 2016.  https://doi.org/10.1016/j.jtho.2016.02.015 Google Scholar
  6. 6.
    Krishnan C, Warnke RA, Arber DA, Natkunam Y (2010) PD-1 expression in T-cell lymphomas and reactive lymphoid entities: potential overlap in staining patterns between lymphoma and viral lymphadenitis. Am J Surg Pathol 34:178–189.  https://doi.org/10.1097/PAS.0b013e3181cc7e79 CrossRefGoogle Scholar
  7. 7.
    van Dongen JJ, Langerak AW, Brüggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia 17:2257–2317.  https://doi.org/10.1038/sj.leu.2403202 CrossRefGoogle Scholar
  8. 8.
    Laurent C, Delas A, Gaulard P, Haioun C, Moreau A, Xerri L, Traverse-Glehen A, Rousset T, Quintin-Roue I, Petrella T, Emile JF, Amara N, Rochaix P, Chenard-Neu MP, Tasei AM, Menet E, Chomarat H, Costes V, Andrac-Meyer L, Michiels JF, Chassagne-Clement C, de Leval L, Brousset P, Delsol G, Lamant L (2016) Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes. Ann Oncol Off J Eur Soc Med Oncol ESMO 27:306–314.  https://doi.org/10.1093/annonc/mdv575 CrossRefGoogle Scholar
  9. 9.
    ten Berge RL, de Bruin PC, Oudejans JJ, Ossenkoppele GJ, van der Valk P, Meijer CJLM (2003) ALK-negative anaplastic large-cell lymphoma demonstrates similar poor prognosis to peripheral T-cell lymphoma, unspecified. Histopathology 43:462–469CrossRefGoogle Scholar
  10. 10.
    Bekkenk MW, Geelen FA, van Voorst Vader PC, Heule F, Geerts ML, van Vloten W, Meijer CJ, Willemze R (2000) Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch cutaneous lymphoma group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment. Blood 95:3653–3661Google Scholar
  11. 11.
    Booken N, Goerdt S, Klemke C-D (2012) Clinical spectrum of primary cutaneous CD30-positive anaplastic large cell lymphoma: an analysis of the Mannheim Cutaneous Lymphoma Registry. J Dtsch Dermatol Ges J Ger Soc Dermatol JDDG 10:331–339.  https://doi.org/10.1111/j.1610-0387.2011.07794.x Google Scholar
  12. 12.
    Aladily TN, Medeiros LJ, Amin MB, Haideri N, Ye D, Azevedo SJ, Jorgensen JL, de Peralta-Venturina M, Mustafa EB, Young KH, You MJ, Fayad LE, Blenc AM, Miranda RN (2012) Anaplastic large cell lymphoma associated with breast implants: a report of 13 cases. Am J Surg Pathol 36:1000–1008.  https://doi.org/10.1097/PAS.0b013e31825749b1 CrossRefGoogle Scholar
  13. 13.
    Aladily TN, Medeiros LJ, Alayed K, Miranda RN (2012) Breast implant-associated anaplastic large cell lymphoma: a newly recognized entity that needs further refinement of its definition. Leuk Lymphoma 53:749–750.  https://doi.org/10.3109/10428194.2011.639020 CrossRefGoogle Scholar
  14. 14.
    Miranda RN, Aladily TN, Prince HM, Kanagal-Shamanna R, de Jong D, Fayad LE, Amin MB, Haideri N, Bhagat G, Brooks GS, Shifrin DA, O'Malley DP, Cheah CY, Bacchi CE, Gualco G, Li S, Keech JA Jr, Hochberg EP, Carty MJ, Hanson SE, Mustafa E, Sanchez S, Manning JT Jr, Xu-Monette ZY, Miranda AR, Fox P, Bassett RL, Castillo JJ, Beltran BE, de Boer JP, Chakhachiro Z, Ye D, Clark D, Young KH, Medeiros LJ (2014) Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol Off J Am Soc Clin Oncol 32:114–120.  https://doi.org/10.1200/JCO.2013.52.7911 CrossRefGoogle Scholar
  15. 15.
    Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, Rimsza L, Pileri SA, Chhanabhai M, Gascoyne RD, Armitage JO, Weisenburger DD, for the International Peripheral T-Cell Lymphoma Project (2008) ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-cell Lymphoma Project. Blood 111:5496–5504.  https://doi.org/10.1182/blood-2008-01-134270 CrossRefGoogle Scholar
  16. 16.
    Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA, Sidhu JS, Hsi ED, Karikehalli S, Jiang L, Vasmatzis G, Gibson SE, Ondrejka S, Nicolae A, Grogg KL, Allmer C, Ristow KM, Wilson WH, Macon WR, Law ME, Cerhan JR, Habermann TM, Ansell SM, Dogan A, Maurer MJ, Feldman AL (2014) ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 124:1473–1480.  https://doi.org/10.1182/blood-2014-04-571091 CrossRefGoogle Scholar
  17. 17.
    Feldman AL, Law M, Remstein ED, Macon WR, Erickson LA, Grogg KL, Kurtin PJ, Dogan A (2009) Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leuk Off J Leuk Soc Am Leuk Res Fund UK 23:574–580.  https://doi.org/10.1038/leu.2008.320 Google Scholar
  18. 18.
    Heo MH, Park HY, Ko YH, Kim WS, Kim SJ (2017) IRF4/MUM1 expression is associated with poor survival outcomes in patients with peripheral T-cell lymphoma. J Cancer 8:1018–1024.  https://doi.org/10.7150/jca.17358 CrossRefGoogle Scholar
  19. 19.
    Zinzani PL, Pellegrini C, Broccoli A et al (2011) Lenalidomide monotherapy for relapsed/refractory peripheral T-cell lymphoma not otherwise specified. Leuk Lymphoma 52:1585–1588.  https://doi.org/10.3109/10428194.2011.573031 CrossRefGoogle Scholar
  20. 20.
    Morschhauser F, Fitoussi O, Haioun C, Thieblemont C, Quach H, Delarue R, Glaisner S, Gabarre J, Bosly A, Lister J, Li J, Coiffier B (2013) A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer Oxf Engl 1990 49:2869–2876.  https://doi.org/10.1016/j.ejca.2013.04.029 Google Scholar
  21. 21.
    Pedersen MB, Hamilton-Dutoit SJ, Bendix K et al (2017) DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study. Blood 130:554–557. Published Online First: 18 May 2017.  https://doi.org/10.1182/blood-2016-12-755496 CrossRefGoogle Scholar
  22. 22.
    Wang X, Boddicker RL, Dasari S, Sidhu JS, Kadin ME, Macon WR, Ansell SM, Ketterling RP, Rech KL, Feldman AL (2017) Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping. Hum Pathol 64:19–27.  https://doi.org/10.1016/j.humpath.2017.01.003 CrossRefGoogle Scholar
  23. 23.
    Han JJ, O’byrne M, Stenson MJ, Maurer MJ, Wellik LE, Feldman AL, McPhail ED, Witzig TE, Gupta M (2018) Prognostic and therapeutic significance of phosphorylated STAT3 and protein tyrosine phosphatase-6 in peripheral-T cell lymphoma. Blood Cancer J 8:110.  https://doi.org/10.1038/s41408-018-0138-8 CrossRefGoogle Scholar
  24. 24.
    Crescenzo R, Abate F, Lasorsa E, Tabbo' F, Gaudiano M, Chiesa N, di Giacomo F, Spaccarotella E, Barbarossa L, Ercole E, Todaro M, Boi M, Acquaviva A, Ficarra E, Novero D, Rinaldi A, Tousseyn T, Rosenwald A, Kenner L, Cerroni L, Tzankov A, Ponzoni M, Paulli M, Weisenburger D, Chan WC, Iqbal J, Piris MA, Zamo' A, Ciardullo C, Rossi D, Gaidano G, Pileri S, Tiacci E, Falini B, Shultz LD, Mevellec L, Vialard JE, Piva R, Bertoni F, Rabadan R, Inghirami G, European T-Cell Lymphoma Study Group, T-Cell Project: Prospective Collection of Data in Patients with Peripheral T-Cell Lymphoma and the AIRC 5xMille Consortium “Genetics-Driven Targeted Management of Lymphoid Malignancies” (2015) Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell 27:516–532.  https://doi.org/10.1016/j.ccell.2015.03.006 CrossRefGoogle Scholar
  25. 25.
    Blombery P, Thompson E, Jones K et al (2016) Whole exome sequencing reveals activating JAK1 and STAT3 mutations in breast-implant associated anaplastic large cell lymphoma. Haematologica 101:e387–e390. Published Online First: 19 May 2016.  https://doi.org/10.3324/haematol.2016.146118 CrossRefGoogle Scholar
  26. 26.
    Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD, Weisenburger DD, Greiner TC, Smith L, Guo S, Wilcox RA, Teh BT, Lim ST, Tan SY, Rimsza LM, Jaffe ES, Campo E, Martinez A, Delabie J, Braziel RM, Cook JR, Tubbs RR, Ott G, Geissinger E, Gaulard P, Piccaluga PP, Pileri SA, Au WY, Nakamura S, Seto M, Berger F, de Leval L, Connors JM, Armitage J, Vose J, Chan WC, Staudt LM, for the Lymphoma Leukemia Molecular Profiling Project and the International Peripheral T-cell Lymphoma Project (2014) Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood 123:2915–2923.  https://doi.org/10.1182/blood-2013-11-536359 CrossRefGoogle Scholar
  27. 27.
    Rassidakis GZ, Thomaides A, Wang S, Jiang Y, Fourtouna A, Lai R, Medeiros LJ (2005) p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma. Leukemia 19:1663–1669.  https://doi.org/10.1038/sj.leu.2403840 CrossRefGoogle Scholar
  28. 28.
    Li HL, Huang XP, Zhou XH, Ji TH, Wu ZQ, Wang ZQ, Jiang HY, Liu FR, Zhao T (2011) Correlation of seven biological factors (Hsp90a, p53, MDM2, Bcl-2, Bax, cytochrome C, and cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma. Biomed Environ Sci BES 24:630–641.  https://doi.org/10.3967/0895-3988.2011.06.007 Google Scholar
  29. 29.
    Jung JT, Kim DH, Kwak EK, Kim JG, Park TI, Sohn SK, Do YR, Kwon KY, Song HS, Park EH, Lee KB (2006) Clinical role of Bcl-2, Bax, or p53 overexpression in peripheral T-cell lymphomas. Ann Hematol 85:575–581.  https://doi.org/10.1007/s00277-006-0127-z CrossRefGoogle Scholar
  30. 30.
    Weilemann A, Grau M, Erdmann T, Merkel O, Sobhiafshar U, Anagnostopoulos I, Hummel M, Siegert A, Hayford C, Madle H, Wollert-Wulf B, Fichtner I, Dörken B, Dirnhofer S, Mathas S, Janz M, Emre NCT, Rosenwald A, Ott G, Lenz P, Tzankov A, Lenz G (2015) Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma. Blood 125:124–132.  https://doi.org/10.1182/blood-2014-08-594507 CrossRefGoogle Scholar
  31. 31.
    Liang X, Branchford B, Greffe B, McGavran L, Carstens B, Meltesen L, Albano EA, Quinones R, Cook B, Graham DK (2013) Dual ALK and MYC rearrangements leading to an aggressive variant of anaplastic large cell lymphoma. J Pediatr Hematol Oncol 35:e209–e213.  https://doi.org/10.1097/MPH.0b013e3182815046 CrossRefGoogle Scholar
  32. 32.
    Monaco S, Tsao L, Murty VV, Nandula SV, Donovan V, Oesterheld J, Bhagat G, Alobeid B (2007) Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phase. Am J Hematol 82:59–64.  https://doi.org/10.1002/ajh.20758 CrossRefGoogle Scholar
  33. 33.
    Wada DA, Law ME, Hsi ED, DiCaudo DJ, Ma L, Lim MS, Souza A, Comfere NI, Weenig RH, Macon WR, Erickson LA, Özsan N, Ansell SM, Dogan A, Feldman AL (2011) Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies. Mod Pathol Off J U S Can Acad Pathol Inc 24:596–605.  https://doi.org/10.1038/modpathol.2010.225 Google Scholar
  34. 34.
    Pham-Ledard A, Prochazkova-Carlotti M, Laharanne E, Vergier B, Jouary T, Beylot-Barry M, Merlio JP (2010) IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases. J Invest Dermatol 130:816–825.  https://doi.org/10.1038/jid.2009.314 CrossRefGoogle Scholar
  35. 35.
    Huang H-S, Liao C-K, Liu T-T, You HL, Wang MC, Huang WT (2018) TP53 mutations in peripheral mature T and NK cell lymphomas: a whole-exome sequencing study with correlation to p53 expression. Hum Pathol 80:145–151.  https://doi.org/10.1016/j.humpath.2018.05.026 CrossRefGoogle Scholar
  36. 36.
    Gallo M, Cacheux V, Vincent L, Bret C, Tempier A, Guittard C, Macé A, Leventoux N, Costes V, Szablewski V (2016) Leukemic non-nodal mantle cell lymphomas have a distinct phenotype and are associated with deletion of PARP1 and 13q14. Virchows Arch Int J Pathol 469:697–706.  https://doi.org/10.1007/s00428-016-2016-8 CrossRefGoogle Scholar
  37. 37.
    Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C (2017) The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia 31:705–711.  https://doi.org/10.1038/leu.2016.263 CrossRefGoogle Scholar
  38. 38.
    Stefancikova L, Moulis M, Fabian P et al (2011) Prognostic impact of p53 aberrations for R-CHOP-treated patients with diffuse large B-cell lymphoma. Int J Oncol 39:1413–1420.  https://doi.org/10.3892/ijo.2011.1170 Google Scholar
  39. 39.
    Shi M, Roemer MGM, Chapuy B, Liao X, Sun H, Pinkus GS, Shipp MA, Freeman GJ, Rodig SJ (2014) Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol 38:1715–1723.  https://doi.org/10.1097/PAS.0000000000000297 CrossRefGoogle Scholar
  40. 40.
    Mitteldorf C, Berisha A, Pfaltz MC, Broekaert SMC, Schön MP, Kerl K, Kempf W (2017) Tumor microenvironment and checkpoint molecules in primary cutaneous diffuse large B-cell lymphoma-new therapeutic targets. Am J Surg Pathol 41:998–1004.  https://doi.org/10.1097/PAS.0000000000000851 CrossRefGoogle Scholar
  41. 41.
    Menguy S, Prochazkova-Carlotti M, Beylot-Barry M, Saltel F, Vergier B, Merlio JP, Pham-Ledard A (2017) PD-L1 and PD-L2 are differentially expressed by macrophages or tumor cells in primary cutaneous diffuse large B-cell lymphoma, leg type. Am J Surg Pathol 42:326–334 Published Online First: 3.  https://doi.org/10.1097/PAS.0000000000000983 CrossRefGoogle Scholar
  42. 42.
    Four M, Cacheux V, Tempier A et al (2017) PD1 and PDL1 expression in primary central nervous system diffuse large B-cell lymphoma are frequent and expression of PD1 predicts poor survival. Hematol Oncol 35:487–496. Published Online First: 13 December 2016.  https://doi.org/10.1002/hon.2375 CrossRefGoogle Scholar
  43. 43.
    Twa DDW, Chan FC, Ben-Neriah S, Woolcock BW, Mottok A, Tan KL, Slack GW, Gunawardana J, Lim RS, McPherson AW, Kridel R, Telenius A, Scott DW, Savage KJ, Shah SP, Gascoyne RD, Steidl C (2014) Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood 123:2062–2065.  https://doi.org/10.1182/blood-2013-10-535443 CrossRefGoogle Scholar
  44. 44.
    Chapuy B, Roemer MGM, Stewart C, Tan Y, Abo RP, Zhang L, Dunford AJ, Meredith DM, Thorner AR, Jordanova ES, Liu G, Feuerhake F, Ducar MD, Illerhaus G, Gusenleitner D, Linden EA, Sun HH, Homer H, Aono M, Pinkus GS, Ligon AH, Ligon KL, Ferry JA, Freeman GJ, van Hummelen P, Golub TR, Getz G, Rodig SJ, de Jong D, Monti S, Shipp MA (2016) Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 127:869–881.  https://doi.org/10.1182/blood-2015-10-673236 CrossRefGoogle Scholar
  45. 45.
    Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Nagano S, Maeda T, Nagata Y, Kitanaka A, Mizuno S, Tanaka H, Chiba K, Ito S, Watatani Y, Kakiuchi N, Suzuki H, Yoshizato T, Yoshida K, Sanada M, Itonaga H, Imaizumi Y, Totoki Y, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Masuda K, Minato N, Kashiwase K, Izutsu K, Takaori-Kondo A, Miyazaki Y, Takahashi S, Shibata T, Kawamoto H, Akatsuka Y, Shimoda K, Takeuchi K, Seya T, Miyano S, Ogawa S (2016) Aberrant PD-L1 expression through 3’-UTR disruption in multiple cancers. Nature 534:402–406.  https://doi.org/10.1038/nature18294 CrossRefGoogle Scholar
  46. 46.
    Atsaves V, Tsesmetzis N, Chioureas D, Kis L, Leventaki V, Drakos E, Panaretakis T, Grander D, Medeiros LJ, Young KH, Rassidakis GZ (2017) PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia 31:1633–1637.  https://doi.org/10.1038/leu.2017.103 CrossRefGoogle Scholar
  47. 47.
    Horlad H, Ma C, Yano H, Pan C, Ohnishi K, Fujiwara Y, Endo S, Kikukawa Y, Okuno Y, Matsuoka M, Takeya M, Komohara Y (2016) An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma. Cancer Sci 107:1696–1704.  https://doi.org/10.1111/cas.13065 CrossRefGoogle Scholar
  48. 48.
    Ma C, Horlad H, Pan C, Yano H, Ohnishi K, Fujiwara Y, Matsuoka M, Lee A, Niidome T, Yamanaka R, Takeya M, Komohara Y (2017) Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines. J Clin Exp Hematop JCEH 57:21–25.  https://doi.org/10.3960/jslrt.17006 CrossRefGoogle Scholar
  49. 49.
    Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, Sugita Y, Yufu Y, Choi I, Abe Y, Uike N, Nagafuji K, Okamura T, Akashi K, Takayanagi R, Shiratsuchi M, Ohshima K (2015) Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood 126:2193–2201.  https://doi.org/10.1182/blood-2015-02-629600 CrossRefGoogle Scholar
  50. 50.
    Xing W, Dresser K, Zhang R, Evens AM, Yu H, Woda BA, Chen BJ (2016) PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications. Oncotarget 7:59976–59986.  https://doi.org/10.18632/oncotarget.11045 Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Anna Gerbe
    • 1
    • 2
  • Melissa Alame
    • 3
    • 2
  • Olivier Dereure
    • 4
    • 2
  • Samia Gonzalez
    • 5
  • Luc Durand
    • 6
  • Ariane Tempier
    • 1
  • Laura De Oliveira
    • 1
  • Alicia Tourneret
    • 1
    • 2
  • Valérie Costes-Martineau
    • 1
    • 2
  • Valère Cacheux
    • 3
    • 2
  • Vanessa Szablewski
    • 1
    • 2
    Email author
  1. 1.Département de Biopathologie Cellulaire et Tissulaire des Tumeurs, CHU MontpellierHôpital Gui De ChauliacMontpellierFrance
  2. 2.Faculté de MédecineUniversité MontpellierMontpellierFrance
  3. 3.Département d’Hématologie biologique, CHU MontpellierHôpital Saint EloiMontpellierFrance
  4. 4.Département de Dermatologie, CHU MontpellierHôpital Saint EloiMontpellierFrance
  5. 5.Département de PathologieCHU Nîmes, CarémeauNîmesFrance
  6. 6.MEDIPATHGrabelsFrance

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