title: Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients.
abstract: OBJECTIVE
  To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients.
  
  
  RESULTS
  The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001).
  
  
  CONCLUSIONS
  Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized.
authors.affiliation: Academic Haematology, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Culpin
authors.forename: Michal
authors.initials: M
authors.lastname: Sieniawski
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Geetha K
authors.initials: GK
authors.lastname: Menon
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Proctor
authors.forename: Paul
authors.initials: P
authors.lastname: Milne
authors.forename: Kate
authors.initials: K
authors.lastname: McCabe
authors.forename: Tryfonia
authors.initials: T
authors.lastname: Mainou-Fowler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D015843:Serpins / Q000378:metabolism; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D058846:Antibodies, Monoclonal, Murine-Derived; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; C571759:R-CHOP protocol; C476825:SERPINA9 protein, human; D015843:Serpins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D015260:Neprilysin; D011241:Prednisone
keywords: N-HL; diffuse large B cell lymphoma; immunohistochemistry; predictive algorithms; prognosis; survival