Gritti Giuseppe, Gianatti Andrea, Petronzelli Fiorella, De Santis Rita, Pavoni Chiara, Rossi Riccardo Lorenzo, Cattaneo Laura, Spagnoli Luigi Giusto, Ferrari Silvia, Rossi Andrea, Barbui Anna Maria, Rambaldi Alessandro
Hematology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Pathology Unit, Ospedale Papa Giovanni XXII, Bergamo, Italy.
Oncotarget. 2018 Jan 3;9(11):9766-9775. doi: 10.18632/oncotarget.23919. eCollection 2018 Feb 9.
The clinical outcome of T-cell non-Hodgkin lymphoma (NHL) is poor and innovative treatments are needed. Tenascin-C is a large extracellular glycoprotein not expressed under physiological conditions, but overexpressed in cancer. Aim of the study was to evaluate tenascin-C expression within pathologic tissue of T-cell NHL and determine its clinical significance. We used an immunohistochemistry approach using the anti-tenascin-C monoclonal antibody Tenatumomab in 75 systemic T-cell NHL (including 72 mature and 3 precursor T-cell NHL), and 25 primary cutaneous T-cell NHL. Data were analyzed in terms of staining intensity, proportion of involved areas and histologic pattern, and results were correlated with clinical characteristics and outcome. Ninety-three percent of the cases were tenascin-C positive and 59% of systemic diseases were characterized by a predominant involvement (>50%). Stromal expression was detected in all the cases while vascular and vascular plus cytoplasmic expression was present in 49% and 23%. The constant overexpression of the tenascin-C gene was observed in two independent publicly available T-cell NHL gene expression datasets. In conclusions, tenascin-C represents an attractive target that sets the rationale to investigate the therapeutic activity of radiolabeled Tenatumomab in T-cell NHL.
T 细胞非霍奇金淋巴瘤（NHL）的临床预后较差，需要创新的治疗方法。腱生蛋白-C 是一种大型细胞外糖蛋白，在生理条件下不表达，但在癌症中过度表达。本研究的目的是评估腱生蛋白-C 在 T 细胞 NHL 病理组织中的表达，并确定其临床意义。我们采用免疫组织化学方法，使用抗腱生蛋白-C 单克隆抗体 Tenatumomab 检测了 75 例系统性 T 细胞 NHL（包括 72 例成熟型和 3 例前体 T 细胞 NHL）以及 25 例原发性皮肤 T 细胞 NHL。根据染色强度、受累区域比例和组织学模式对数据进行分析，并将结果与临床特征和预后相关联。93%的病例腱生蛋白-C 呈阳性，59%的系统性疾病以主要受累（>50%）为特征。所有病例均检测到基质表达，而血管和血管加细胞质表达分别见于 49%和 23%的病例。在两个独立的公开可用 T 细胞 NHL 基因表达数据集中均观察到腱生蛋白-C 基因的持续过度表达。总之，腱生蛋白-C 是一个有吸引力的靶点，为研究放射性标记的 Tenatumomab 在 T 细胞 NHL 中的治疗活性提供了理论依据。
