Sakuma Hidenori, Nakamura Tsuneya, Uemura Naomi, Chiba Tsutomu, Sugiyama Toshiro, Asaka Masahiro, Akamatsu Taiji, Ueda Ryuzo, Eimoto Tadaaki, Goto Hidemi, Nakamura Shigeo, Inagaki Hiroshi
Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Mod Pathol. 2007 Apr;20(4):460-6. doi: 10.1038/modpathol.3800758. Epub 2007 Mar 2.
The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication-resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P=0.0094) and Group C (2/12 cases, 17%, P=0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pylori-associated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria.
大多数胃黏膜相关淋巴组织（MALT）淋巴瘤仅通过根除幽门螺杆菌就能成功治愈。然而，这些肿瘤的某些亚组对根除治疗具有抗性。由于API2-MALT1融合是其中一个亚组的特征，我们将胃MALT淋巴瘤分为三组：根除反应性且API2-MALT1融合阴性（A组）、根除抗性且融合阴性（B组）以及根除抗性且融合阳性（C组）。为了进一步表征胃MALT淋巴瘤，我们通过对45例病例的单克隆PCR产物进行广泛亚克隆，分析了在肿瘤进展过程中不变的VH基因。与B组（1/10例，10%，P = 0.0094）和C组（2/12例，17%，P = 0.017）相比，A组肿瘤优先使用VH3-23和VH3-30（14/23例，61%）。B组和C组肿瘤使用多样化的VH片段，未发现优势VH片段。大多数病例中检测到体细胞突变。按照确认突变的严格标准评估时，45例中有3例（7%）检测到正在发生的突变。这些发现表明，炎症依赖性肿瘤（A组）可能源自高度受限的、可能与幽门螺杆菌相关的B细胞亚群，且可能不常进展为炎症非依赖性肿瘤（B组和C组）。尽管在这种肿瘤中被认为很常见，但按照严格标准评估时，正在发生的突变可能并不常见。
