title: Prognostic value of cell-cycle markers in ocular adnexal lymphoma: an assessment of 230 cases.
abstract: BACKGROUND
  To determine the prognostic value of cell-cycle associated markers in ocular adnexal lymphoma (OAL).
  
  
  METHODS
  Two hundred sixty-one consecutive cases of ocular adnexal lymphoproliferative lesions were subdivided into reactive lymphoid hyperplasia (RLH), atypical lymphoid hyperplasia (ALH) and OAL. The latter were sub-typed according to the new WHO Lymphoma Classification. All lesions were investigated applying standard immunohistochemical methods with antibodies specific for pRB, p53, p16, p21, BCL-6 and for multiple myeloma oncogene-1-protein (MUM1, also known as IRF4). The main endpoints included the development of a local recurrence, of systemic disease and of lymphoma-related death. The association of prognostic variables with endpoints was assessed by multiple logistic and Cox regression models, respectively.
  
  
  RESULTS
  The ocular adnexal lymphoproliferative lesions were categorised as OAL ( n=230; 88%), RLH ( n=29; 11%), and ALH ( n=2; 1%). The major lymphoma subtypes included 136 extranodal marginal zone B-cell lymphoma (EMZL), 31 diffuse large cell B-cell lymphomas, 27 follicular lymphomas, 9 plasmacytomas, 9 lymphoplasmocytic lymphoma/immunocytomas and 8 mantle cell lymphomas. The median follow-up time was 44.5 months. Most OAL patients had Stage IE disease and were treated with radiotherapy. Thirty-seven (25%) Stage IE patients had tumour relapses: these were significantly associated with an increased BCL6 blast percentage. Sixty-two (42%) Stage IE patients developed systemic disease: they had "non-EMZL" with large growth fractions and increased blast percentages for BCL6. Fifty-seven (25%) OAL patients died because of their lymphoma; lymphoma-related death was significantly associated on multivariable analysis with advanced clinical stage, an age >60 years and large tumour growth fractions.
  
  
  CONCLUSIONS
  Subtyping of OAL according to the new WHO Lymphoma Classification, the stage of disease and tumour cell growth fraction aided the prediction of (1) tumour relapse, (2) the development of systemic disease and (3) lymphoma-related death in OAL.
authors.affiliation: Department of Pathology, University Hospital Benjamin Franklin of the Free University, Hindenburgdamm 30, 12200, Berlin, Germany. secoupland@yahoo.de.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Coupland
authors.affiliation: Department of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Department of Ophthalmology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Auw-Haedrich
authors.affiliation: Department of Pathology, Western Infirmary, Glascow, Scotland.
authors.forename: William R
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Department of Pathology, University Hospital Benjamin Franklin of the Free University, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003230:Conjunctival Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D005142:Eyelid Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009918:Orbital Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019310:Pseudolymphoma / Q000145:classification / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins