TY - JOUR
T1 - The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma
AU - Brandt, Simone
AU - Montagna, Chiara
AU - Georgis, Antoin
AU - Schüffler, Peter J.
AU - Bühler, Marco M.
AU - Seifert, Burkhardt
AU - Thiesler, Thore
AU - Curioni-Fontecedro, Alessandra
AU - Hegyi, Ivan
AU - Dehler, Silvia
AU - Martin, Vittoria
AU - Tinguely, Marianne
AU - Soldini, Davide
N1 - Funding Information:
We are grateful to Martina Storz for excellent technical assistance, as well as to the team of the “Cancer Registry” for invaluable support. DS was supported by the Swiss National Science Foundation and by the Swiss Cancer League and MT by the Cancer League of the Canton of Zurich.
PY - 2013/10/8
Y1 - 2013/10/8
N2 - 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.
AB - 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.
KW - DLBCL
KW - Extracellular matrix
KW - Fibronectin
KW - SPARC
KW - Stromal signature
KW - Tumour microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84978025210&partnerID=8YFLogxK
U2 - 10.1186/2162-3619-2-27
DO - 10.1186/2162-3619-2-27
M3 - Article
AN - SCOPUS:84978025210
SN - 2162-3619
VL - 2
JO - Experimental Hematology and Oncology
JF - Experimental Hematology and Oncology
IS - 1
M1 - 27
ER -
