The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma.
BACKGROUND
In diffuse large B-cell lymphomas, gene expression profiling studies attributed a major biologic role to non-neoplastic cells of the tumour microenvironment as its composition and characteristics were shown to predict survival. In particular, the expression of selected genes encoding components of the extracellular matrix was reported to be associated with clinical outcome. Nevertheless, the translation of these data into robust, routinely applicable immunohistochemical markers is still warranted. Therefore, in this study, we analysed the combination of the expression of the extracellular matrix components Fibronectin and SPARC on formalin-fixed paraffin embedded tissue derived from 173 patients with DLBCL in order to recapitulate gene expression profiling data.


RESULTS
The expression of Fibronectin and SPARC was detected in 77/173 (44.5%) and 125/173 (72.3%) cases, respectively, and 55/173 (31.8%) cases were double positive. Patients with lymphomas expressing Fibronectin showed significantly longer overall survival when compared to negative ones (6.3 versus 3.6 years). Moreover, patients with double positive lymphomas also presented with significantly longer overall survival when compared with the remaining cases (11.6 versus 3.6 years) and this combined expression of both markers results in a better association with overall survival data than the expression of SPARC or Fibronectin taken separately (Hazard ratio 0.41, 95% confidence interval 0.17 to 0.95, p = 0.037). Finally, neither Fibronectin nor SPARC expression was associated with any of the collected clinico-pathological parameters.


CONCLUSIONS
The combined immunohistochemical assessment of Fibronectin and SPARC, two components of the extracellular matrix, represents an important tool for the prediction of survival in diffuse large B-cell lymphomas. Our study suggests that translation of gene expression profiling data on tumour microenvironment into routinely applicable immunohistochemical markers is a useful approach for a further characterization of this heterogeneous type of lymphoma.
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Simone
S
Brandt
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Chiara
C
Montagna
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Antoin
A
Georgis
Department of Computer Science, ETH Zurich, Zurich, Switzerland.
Peter J
PJ
Schüffler
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Marco M
MM
Bühler
Division of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
Burkhardt
B
Seifert
Institute of Pathology, University of Bonn, Bonn, Germany.
Thore
T
Thiesler
Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
Alessandra
A
Curioni-Fontecedro
Institute of Pathology, Locarno, Switzerland.
Ivan
I
Hegyi
Cancer Registry, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Silvia
S
Dehler
Institute of Pathology, Locarno, Switzerland.
Vittoria
V
Martin
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.|Kempf and Pfaltz, Histologische Diagnostik, Zurich 8042, Switzerland.
Marianne
M
Tinguely
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Davide
D
Soldini