Identification of outcome predictors in diffuse large B-cell lymphoma. Immunohistochemical profiling of homogeneously treated de novo tumors with nodal presentation on tissue micro-arrays.
OBJECTIVE
Patients with diffuse large B-cell lymphoma (DLBCL) could benefit from integration of well-established bioclinical prognostic factors with new tools - such as micro-arrays - exploring aberrant gene and/or protein expression.


METHODS
Tissue micro-arrays (TMA) were constructed for the paraffin blocks of 68 patients with de novo DLBCL with nodal presentation, who underwent MACOP-B and were provided with complete clinical information. TMA were tested with specific antibodies against CD10, CD20, CD30, CD79a, CD138, Bcl-2, Bcl-6, IRF4, and IRTA1.


RESULTS
The following phenotypic subclassification was made: a) CD10 +/Bcl-6 + or Bcl-6+/IRF4 +, but Bcl-2-/CD30-/CD138-- suggesting B-cells gathering/leaving the germinal center (group 1; n=36); b) Bcl-2+/CD10-/Bcl-6- and CD30+ or CD138+ corresponding to putative non-germinal center B-cells with features of activation or plasmablastic/plasmacellular differentiation (group 2; n=17); c) CD30-/CD138- with extensive Bcl-2 positivity and variable CD10, Bcl-6 and IRF4 combinations (group 3; n=15). Mean IPI scores were 0.6, 1.9 and 1.1 for groups 1, 2 and 3, respectively (p= 0.001). Complete remission (CR) rates were 89%, 53% and 73% (p= 0.015). The 3-year relapse-free survival (RFS) rates are 86%, 41% and 63% (p=0.001) and 42-month overall survival (OS) rates are 91%, 38% and 66% (p=0.0002).


CONCLUSIONS
The present TMA-based study suggests an immunophenotypic profiling system for patients with de novo DLBCL that seems to provide additional prognostic information and contributes to the existing debate on the identification of suitable immunohistochemical surrogates of gene expression profiling results.
Zinzani
Pier Luigi
PL
Pathologic Anatomy & Lymphoma Unit, Institute of Haematology and Medical Oncology L. & A. Seràgnoli, Bologna University, Bologna, Italy. plzinzo@med.unibo.it
Dirnhofer
Stephan
S
Sabattini
Elena
E
Alinari
Lapo
L
Piccaluga
Pier Paolo
PP
Stefoni
Vittorio
V
Tani
Monica
M
Musuraca
Gerardo
G
Marchi
Enrica
E
Falini
Brunangelo
B
Baccarani
Michele
M
Pileri
Stefano A
SA
D000328:Adult; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D040081:Protein Array Analysis; D016019:Survival Analysis