Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients

• Published in: Histopathology Vol. 63; no. 6; pp. 788 - 801
• Main Authors: Culpin, Rachel E, Sieniawski, Michal, Angus, Brian, Menon, Geetha K, Proctor, Stephen J, Milne, Paul, McCabe, Kate, Mainou-Fowler, Tryfonia
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2013; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biomarkers, Tumor - metabolism; Cohort Studies; Combined Modality Therapy; Cyclophosphamide - administration & dosage; diffuse large B cell lymphoma; Disease-Free Survival; DNA-Binding Proteins - metabolism; Doxorubicin - administration & dosage; Female; Humans; Immunohistochemistry; Immunotherapy; Kaplan-Meier Estimate; LIM Domain Proteins - metabolism; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Multivariate analysis; N-HL; Neoplasm Proteins - metabolism; Neprilysin - metabolism; predictive algorithms; Prednisone - administration & dosage; Prognosis; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-bcl-6; Rituximab; Serpins - metabolism; survival; Vincristine - administration & dosage; Young Adult; immunohistochemistry; predictive algorithms; diffuse large B cell lymphoma; prognosis; N-HL; survival
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12223

Aims To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy‐treated diffuse large B cell lymphoma patients. Methods and 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.