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

Histopathology. 2013 Dec;63(6):788-801. doi: 10.1111/his.12223. Epub 2013 Oct 1.

Abstract

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.

Keywords: N-HL; diffuse large B cell lymphoma; immunohistochemistry; predictive algorithms; prognosis; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • DNA-Binding Proteins / metabolism
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Immunohistochemistry
  • Immunotherapy*
  • Kaplan-Meier Estimate
  • LIM Domain Proteins / metabolism
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / therapy*
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neprilysin / metabolism
  • Prednisone / administration & dosage
  • Prognosis
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-6
  • Rituximab
  • Serpins / metabolism
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal, Murine-Derived
  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO2 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • R-CHOP protocol
  • SERPINA9 protein, human
  • Serpins
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Neprilysin
  • Prednisone