title: Diagnostic Utility of the Germinal Center-associated Markers GCET1, HGAL, and LMO2 in Hematolymphoid Neoplasms.
abstract: Implementation of new phenotypic markers in routine diagnostics of hematolymphoid neoplasms is a challenging task with a plethora of potentially relevant proteins. We investigated 3 recently discovered proteins expressed in the germinal centers of lymph nodes (LMO2, GCET1, and HGAL) in a compilation of leukemia, lymphoma, and thymic tumor entities. Altogether, 1590 cases (1519 on tissue microarrays, 71 on conventional slides) were included. Expressions of LMO2, GCET1, and HGAL were investigated by immunohistochemistry, evaluated for their differential diagnostic relevance, and correlated with the clinical outcome of patients. In Hodgkin lymphoma (HL), the expression of LMO2, GCET1, and HGAL could be largely seen in tumor cells of nodular lymphocyte predominant HL (NLPHL) but only occasionally in classic HL. The majority of B-cell lymphoma cases was positive for LMO2 [except for Burkitt lymphoma (BL)] and HGAL with weaker to moderate staining intensity, compared with the intensely staining follicular lymphomas (FL). Except for FL (60% of cases) and diffuse large B-cell lymphomas (DLBCL, 36% of cases), all other B-cell lymphomas expressed little or no GCET1. In thymomas, the non-neoplastic immature T-cells were LMO2-negative, whereas the neoplastic lymphoblasts were LMO2-positive in more than half of the lymphoblastic lymphomas (LBL). Our findings provide new potential assistance in the differential diagnosis of FL to marginal zone lymphoma, classic HL to NLPHL and primary mediastinal B-cell lymphoma, DLBCL to BL, and thymoma to LBL. Finally, HGAL proved to be a prognostic marker for classic HL regarding the background population and in DLBCL regarding the tumor cells.
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Menter
authors.forename: Anjes
authors.initials: A
authors.lastname: Gasser
authors.forename: Darius
authors.initials: D
authors.lastname: Juskevicius
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D005260:Female; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins / Q000378:metabolism*; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C476824:GCSAM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C476825:SERPINA9 protein, human; D015843:Serpins