TY - JOUR A1 - Schümann, Franziska Lea A1 - Groß, Elisabeth A1 - Bauer, Marcus A1 - Rohde, Christian A1 - Sandmann, Sarah A1 - Terziev, Denis A1 - Müller, Lutz P. A1 - Posern, Guido A1 - Wienke, Andreas A1 - Fend, Falko A1 - Hansmann, Martin-Leo A1 - Klapper, Wolfram A1 - Rosenwald, Andreas A1 - Stein, Harald A1 - Dugas, Martin A1 - Müller-Tidow, Carsten A1 - Wickenhauser, Claudia A1 - Binder, Mascha A1 - Weber, Thomas T1 - Divergent effects of EZH1 and EZH2 protein expression on the prognosis of patients with T-cell lymphomas JF - Biomedicines N2 - T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients. KW - T-cell non-Hodgkin's lymphomas KW - PTCL KW - epigenetics KW - EZH1 KW - EZH2 KW - H3K27me3 KW - immunohistochemistry KW - next generation sequencing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252155 SN - 2227-9059 VL - 9 IS - 12 ER - TY - JOUR A1 - Maas, Moritz A1 - Mischinger, Johannes A1 - Compérat, Eva A1 - Scharpf, Marcus A1 - Fend, Falko A1 - Todenhöfer, Timlan A1 - Stenzl, Arnulf A1 - Gakis, Georgios A1 - Rausch, Steffen T1 - Utility of pT3 substaging in lymph node-negative urothelial carcinoma of the bladder: do pathologic parameters add to prognostic sub-stratification? JF - World Journal of Urology N2 - Purpose The value of bladder cancer (BC) substaging into macroscopic (pT3b) and microscopic (pT3a) perivesical fat extension in lymph node (Ln)-negative patients is controversially discussed and limited evidence for prognostic relevance of additional histopathological factors in pT3 BC exists. We evaluated the prognostic value of pT3 substaging and established pathological and clinical parameters with focus on tumor invasive front (TIF) and tumor size. Methods Specimens of 52 patients treated with radical cystectomy (RC) for pT3 a/b muscle-invasive BC were reviewed and re-evaluated by a pathologist specialized in uropathology. Clinical variables and standard histopathologic characteristics were assessed including TIF and tumor size. Their value as prognosticators for overall survival (OS) and recurrence-free survival (RFS) was evaluated. Results Mean age of patients was 67.55 years. Tumors were staged pT3a in 28 patients (53.8%) and pT3b in 24 (46.8%). Median OS was 34.51 months. Median tumor size was 3.2 cm, median TIF was 11.0 mm. Differences in OS between pT3a and pT3b were not significant (p = 0.45). Carcinoma in situ (CIS) and lymphovascular invasion (LVI) were significantly associated with pT3b tumors. Univariate analysis could not identify pathological prognosticators like TIF or tumor size for OS and RFS (p for all > 0.05). Conclusion No significant differences in OS or RFS were observed comparing Ln-negative pT3 BC following radical cystectomy. Additional pathologic variables like TIF could not be identified as prognosticator. Relevance of pT3 BC substaging needs reevaluation in larger prospective cohorts. KW - tumor invasion front KW - muscle-invasive bladder cancer KW - pathological staging KW - patient outcome KW - perivesical extension Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266535 SN - 1433-8726 VL - 39 IS - 11 ER - TY - JOUR A1 - Hartmann, Sylvia A1 - Plütschow, Annette A1 - Mottok, Anja A1 - Bernd, Heinz‐Wolfram A1 - Feller, Alfred C. A1 - Ott, German A1 - Cogliatti, Sergio A1 - Fend, Falko A1 - Quintanilla‐Martinez, Leticia A1 - Stein, Harald A1 - Klapper, Wolfram A1 - Möller, Peter A1 - Rosenwald, Andreas A1 - Engert, Andreas A1 - Hansmann, Martin‐Leo A1 - Eichenauer, Dennis A. T1 - The time to relapse correlates with the histopathological growth pattern in nodular lymphocyte predominant Hodgkin lymphoma JF - American Journal of Hematology N2 - Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first‐line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies. Among the 33 GHSG patients, 21 patients presented with a typical growth pattern at initial diagnosis, whereas 12 patients had a variant histology. The histopathological growth patterns at initial diagnosis and at relapse were consistent in 67% of cases. A variant histology at initial diagnosis was associated with a shorter median time to lymphoma recurrence (2.8 vs 5.2 years; P = .0219). A similar tendency towards a shorter median time to lymphoma recurrence was observed for patients presenting with a variant histology at relapse, irrespective of the growth pattern at initial diagnosis. Results obtained from the 41 NLPHL patients who had been treated outside GHSG studies were comparable (median time to lymphoma recurrence for variant histology vs typical growth pattern at initial diagnosis: 1.5 vs 7.0 years). In conclusion, the histopathological growth pattern remains consistent at relapse in the majority of NLPHL cases, and has major impact on the time of relapse. KW - Hodgkin lymphoma KW - relapse KW - growth patterns Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212594 VL - 94 IS - 11 SP - 1208 EP - 1213 ER - TY - JOUR A1 - Zamò, Alberto A1 - Johnston, Peter A1 - Attygalle, Ayoma D A1 - Laurent, Camille A1 - Arber, Daniel A A1 - Fend, Falko T1 - Aggressive B‐cell lymphomas with a primary bone marrow presentation JF - Histopathology KW - aggressive B‐cell lymphoma KW - bone marrow biopsy KW - bone marrow–spleen–liver large B‐cell lymphoma KW - diffuse large B‐cell lymphoma KW - EAHP/SH bone marrow workshop KW - high‐grade B‐cell lymphoma KW - intravascular large B‐cell lymphoma KW - primary bone marrow presentation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218327 VL - 77 IS - 3 SP - 369 EP - 379 ER - TY - JOUR A1 - Wang, Huiqiang A1 - Chen, Nanhai G. A1 - Minev, Boris R. A1 - Zimmermann, Martina A1 - Aguilar, Richard J. A1 - Zhang, Qian A1 - Sturm, Julia B. A1 - Fend, Falko A1 - Yu, Yong A. A1 - Cappello, Joseph A1 - Lauer, Ulrich M. A1 - Szalay, Aladar A. T1 - Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains JF - PLoS ONE N2 - Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease. KW - lymph nodes KW - cancer treatment KW - metastatic tumors KW - breast cancer KW - blood KW - prostate cancer KW - ascites KW - mouse models Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130059 VL - 8 IS - 9 ER - TY - JOUR A1 - Schraven, Sebastian P. A1 - Plontke, Stefan K. A1 - Syha, Roland A1 - Fend, Falko A1 - Wolburg, Hartwig A1 - Adam, Patrick T1 - Dendritic cell tumor in a salivary gland lymph node: a rare differential diagnosis of salivary gland neoplasms N2 - Dendritic cell tumors are extremely rare neoplasms arising from antigen-presenting cells of the immune system. We report a case of a 69-year-old man with an unremarkable medical history who presented with a 2-months history of a gradually enlarging painless, firm, mobile, 2 × 2-cm swelling at the caudal pole of the left parotid gland without systemic symptoms. Histologically, the tumor consisted of a spindle cell proliferation in an intraparotideal lymph node. Based on the histopathologic, immunohistochemical and electron microscopic findings, a dendritic cell tumor, not otherwise specified (NOS) in an intraparotideal lymph node was diagnosed. The patient underwent complete tumor resection, and is currently free of disease, 2 years after surgery. These extremely rare tumors must be distinguished from other more common tumors in the salivary glands. Awareness that dendritic cell tumors may occur in this localization, careful histologic evaluation and ancillary immunohistochemical and electron microscopical analyses should allow for recognition of this entity. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1614859498581601. KW - Medizin KW - Dendritic cell tumor KW - salivary gland lymph node Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69190 ER -