Department of Oncology and.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Blood. 2017 Jan 12;129(2):188-198. doi: 10.1182/blood-2016-04-713719. Epub 2016 Nov 18.
We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (DLBCL[MALT]) and without ("pure" DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of cytotoxin-associated gene A (CagA) and CagA-signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p-SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated with HP dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored. The association between expression of CagA, p-SHP-2, and p-ERK in malignant B cells and tumor response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive gastric DLBCL who received HPE as frontline treatment. We detected CagA expression in 20 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% vs 75.9%) and an increased specificity (84.0% vs 75.0%) for HP dependence compared with CagA expression alone. Our results indicated that CagA and its signaling molecules can be detected in the malignant B cells of gastric DLBCL, and the expression of these molecules is clinically and biologically associated with HP dependence.
我们之前报道称，早期胃弥漫性大 B 细胞淋巴瘤（DLBCL），包括黏膜相关淋巴组织（MALT）DLBCL 和不具有（“纯”）MALT 淋巴瘤特征的 DLBCL，在一线幽门螺杆菌（HP）根除（HPE）后可以实现长期完全缓解。我们最近报道称，细胞毒素相关基因 A（CagA）和 CagA 信号分子（磷酸-Src 同源-2 结构域含磷酶 [p-SHP2]和磷酸细胞外信号调节激酶 [p-ERK]）的表达与胃 MALT 淋巴瘤的 HP 依赖性相关。然而，CagA 和 CagA 信号分子在胃 DLBCL 中的意义仍未得到探索。在 63 例接受 HPE 作为一线治疗的 IE/IIE1 期 HP 阳性胃 DLBCL 患者中，评估了恶性 B 细胞中 CagA、p-SHP-2 和 p-ERK 的表达与 HPE 肿瘤反应之间的关系。我们在 42 例 DLBCL（MALT）病例中的 20 例（47.6%）和 21 例“纯”DLBCL 病例中的 13 例（61.9%）中检测到 CagA 的表达。在 HP 依赖性肿瘤中，CagA 的表达高于非依赖性肿瘤（74.3%[26/35] vs 25.0%[7/28]）。表达 CagA 的患者对 HPE 的反应比不表达 CagA 的患者更快（完全缓解的中位时间，4.0 个月 vs 5.0 个月）。CagA 的表达与 p-SHP-2 和 p-ERK 的表达密切相关。与单独 CagA 表达相比，CagA、p-SHP-2 和 p-ERK 的联合表达对 HP 依赖性具有更高的阳性预测值（81.8% vs 75.9%）和特异性（84.0% vs 75.0%）。我们的研究结果表明，胃 DLBCL 中的恶性 B 细胞中可以检测到 CagA 及其信号分子，这些分子的表达与 HP 依赖性具有临床和生物学关联。
