Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Department of Computer Science, ETH Zurich, Zurich, Switzerland.
Exp Hematol Oncol. 2013 Oct 8;2(1):27. doi: 10.1186/2162-3619-2-27.
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.
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.
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.
在弥漫性大 B 细胞淋巴瘤中，基因表达谱研究将肿瘤微环境中的非肿瘤细胞赋予了重要的生物学作用，因为其组成和特征被证明可以预测生存。特别是，编码细胞外基质成分的某些基因的表达与临床结局相关。然而，将这些数据转化为可靠的、常规应用的免疫组织化学标志物仍然是必要的。因此，在这项研究中，我们分析了来自 173 例弥漫性大 B 细胞淋巴瘤患者的福尔马林固定石蜡包埋组织中细胞外基质成分纤连蛋白和 SPARC 的表达组合，以重现基因表达谱分析数据。
分别有 77/173（44.5%）和 125/173（72.3%）例病例检测到纤连蛋白和 SPARC 的表达，55/173（31.8%）例为双阳性。与阴性组相比，表达纤连蛋白的淋巴瘤患者的总生存率显著延长（6.3 年与 3.6 年）。此外，双阳性淋巴瘤患者的总生存率也显著长于其余病例（11.6 年与 3.6 年），与单独表达 SPARC 或纤连蛋白相比，这两种标志物的联合表达与总生存率数据的相关性更好（风险比 0.41，95%置信区间 0.17 至 0.95，p=0.037）。最后，纤连蛋白和 SPARC 的表达均与所收集的临床病理参数无关。
细胞外基质的两个成分纤连蛋白和 SPARC 的联合免疫组织化学评估是预测弥漫性大 B 细胞淋巴瘤患者生存的重要工具。我们的研究表明，将肿瘤微环境的基因表达谱数据转化为常规应用的免疫组织化学标志物是进一步描述这种异质性淋巴瘤的一种有用方法。
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