title: PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas.
abstract: Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is down-regulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.
authors: Surgical Pathology Unit, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.|Pathology Unit, Second University of Naples, Naples, Italy.
authors: Renato
authors: R
authors: Franco
authors: Surgical Pathology Unit, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Giosuè
authors: G
authors: Scognamiglio
authors: Surgical Pathology Unit, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Elena
authors: E
authors: Valentino
authors: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.
authors: Michela
authors: M
authors: Vitiello
authors: Animal Facility, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Antonio
authors: A
authors: Luciano
authors: Animal Facility, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Giuseppe
authors: G
authors: Palma
authors: Animal Facility, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Claudio
authors: C
authors: Arra
authors: Surgical Pathology Unit, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Elvira
authors: E
authors: La Mantia
authors: Pathology Unit, Hospital 'S.G. Moscati', Avellino, Italy.
authors: Luigi
authors: L
authors: Panico
authors: Pathology Unit, Hospital 'S.G. Moscati', Avellino, Italy.
authors: Valentina
authors: V
authors: Tenneriello
authors: Haematology-Oncology and Stem Cell Transplantation Unit, Department of Hematology, National Cancer Institute, Fondazione 'G. Pascale', IRCCS, Naples, Italy.
authors: Antonello
authors: A
authors: Pinto
authors: Haematology-Oncology and Stem Cell Transplantation Unit, Department of Hematology, National Cancer Institute, Fondazione 'G. Pascale', IRCCS, Naples, Italy.
authors: Ferdinando
authors: F
authors: Frigeri
authors: Haematology-Oncology and Stem Cell Transplantation Unit, Department of Hematology, National Cancer Institute, Fondazione 'G. Pascale', IRCCS, Naples, Italy.
authors: Gaetana
authors: G
authors: Capobianco
authors: Surgical Pathology Unit, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Gerardo
authors: G
authors: Botti
authors: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.
authors: Laura
authors: L
authors: Cerchia
authors: Surgical Pathology Unit, National Cancer Institute 'Fondazione Giovanni Pascale', IRCCS, Naples, Italy.
authors: Annarosaria
authors: A
authors: De Chiara
authors: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.
authors: Monica
authors: M
authors: Fedele
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D018345:Mice, Knockout; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C084103:BCL6 protein, human; D051741:Kruppel-Like Transcription Factors; C412784:PATZ1 protein, human; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein
keywords: DLBCL; PATZ1; non-Hodgkin lymphomas; prognostic marker; tissue-microarray