title: Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene.
abstract: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) of follicular helper T-cell origin and is rare in Taiwan. There are overlapping features of AITL and peripheral T-cell lymphoma with a follicular growth pattern (PTCL-F). Around one fifth of PTCL-F exhibits t(5;9)(q33;q22)/ITK-SYK chromosomal translocation, which is essentially absent in AITL. We retrospectively investigated 35 cases of AITL from Taiwan with histopathology review, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBV) and fluorescence in situ hybridization (FISH) for t(5;9)(q33;q22)/ITK-SYK and correlated the results with overall survival. Twenty-six cases of not otherwise specified PTCL (PTCL-NOS) were also examined by FISH for comparison. Most AITL patients were male (69%) and elderly (median age at 67 years) with frequent bone marrow involvement (53%), high Ann Arbor stages (77%), and elevated serum lactate dehydrogenase (68%). Most cases (80%) showed a typical CD4+/CD8- phenotype and in 90% cases there were scattered EBV-positive B-cells (less than 10% cells). None of these cases showed t(5;9)(q33;q22)/ITK-SYK translocation by FISH. Gain of ITK and SYK gene was identified in 38% and 14% tumors, respectively, but both were not associated with overall survival. Performance status < 2 was associated with a better outcome but not the other clinicopathological factors. All PTCL-NOS cases were negative for ITK-SYK translocation with similar rates (38% and 12%, respectively) of gains at ITK and SYK loci as that of AITL. In this so far the largest series of AITL from Taiwan, we reported the clinicopathological features and FISH findings on ITK and SYK genes. We confirmed the absence of t(5;9)(q33;q22)/ITK-SYK translocation, which may serve as an additional differential diagnostic tool from PTCL-F when present. PTCL-NOS shared a similar pattern of ITK and SYK gains with AITL. More studies are warranted to elucidate the roles of SYK and ITK and other genes in the lymphomagenesis of AITL in Taiwan.
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Peir-In
authors.initials: PI
authors.lastname: Liang
authors.affiliation: Department of Pathology, Chi-Mei Medical Center and Department of Nursing, National Tainan Institute of Nursing Tainan, Taiwan.
authors.forename: Sheng-Tsung
authors.initials: ST
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University and Faculty of Renal Care, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Lin
authors.affiliation: Department of Pathology, Chi-Mei Medical Center and Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology Tainan, Taiwan.
authors.forename: Yen-Chuan
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Department of Pathology, St. Martin De Porres Hospital, Chiayi and School of Medicine, Fu-Jen Catholic University New Taipei City, Taiwan.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.affiliation: Department of Surgical Pathology, Changhua Christian Hospital, Changhua, School of Medicine, Chung Shan Medical University Taichung, Taiwan ; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management Miaoli, Taiwan.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Pathology, E-Da Hospital/I-Shou University Kaohsiung, Taiwan.
authors.forename: Kai-Jen
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Department of Pathology, Sin-Lau Christian Hospital Tainan, Taiwan.
authors.forename: Yun-Chih
authors.initials: YC
authors.lastname: Jung
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Chung-Shan Medical University Hospital and School of Medicine, Chung-Shan Medical University Taichung, Taiwan.
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hwang
authors.affiliation: Division of Hemato-Oncology, Department of Internal Medicine, Chi-Mei Medical Center Liouying, Tainan, Taiwan.
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Huang
authors.affiliation: Department of Pathology, Mackay Medical College and Mackay Memorial Hospital, Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, and Institute of Clinical Medicine, National Yang-Ming University Taipei, Taiwan.
authors.forename: Wei-Chin
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Histopathology, Royal National Orthopaedic Hospital NHS, Middlesex, United Kingdom and Cancer Hospital of Guangxi Medical University Nanning, P. R. China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan, Taipei Medical University and National Taiwan University Taipei, Taiwan.
authors.forename: Shih-Sung
authors.initials: SS
authors.lastname: Chuang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002895:Chromosomes, Human, Pair 5; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D000072377:Syk Kinase; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D014178:Translocation, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C080813:emt protein-tyrosine kinase
keywords: Angioimmunoblastic T-cell lymphoma; ITK; SYK; Taiwan; follicular T-cell lymphoma; follicular helper T-cell; peripheral T-cell lymphoma