Oncogenesis and clinicopathologic characteristics of MALT lymphoma

AP12-MALT1融合基因是黏膜相关淋巴组织（MALT）淋巴瘤的特异性基因。我们最近描述了这种裂变基因的多重RT-PCR测定，可以适用于石蜡切片。通过这个实验，我们明确了肺、皮肤、眼附件、结肠和胃的MALT淋巴瘤的临床病理意义。在41%的肺MALT淋巴瘤病例中检测到融合基因。融合基因阳性肿瘤患者很少有自身免疫性疾病，其LDH水平通常正常。组织学上，融合阳性肿瘤是典型的MALT淋巴瘤，并与核BCL10表达相关（Am J Pathol, 2003）。24例亚洲皮肤MALT淋巴瘤API2-MALT1融合和伯氏螺旋体感染呈阴性。然而，与融合基因密切相关的核BCL10表达在肿瘤中经常被检测到，并与宏观结节性病变有关（Am J Surg Pathol, 2003）。MALT淋巴瘤：13%的眼附件瘤显示API2-MALT1融合。这些阳性病例通常表现出其他染色体异常，这表明一些融合阳性的眼部MALT淋巴瘤可能会发展为高级别淋巴瘤（Mod Pathol, 2003）。结肠MALT淋巴瘤在15%的病例中显示API2-MALT1融合。融合基因常见于男性患者，且与晚期临床阶段相关。后一项观察结果表明，可能需要对融合阳性的结肠MALT淋巴瘤进行密切随访（Mod Pathol, 2003）。一项涉及多器官的胃MALT淋巴瘤的分析显示，这些病例经常出现API2-MALT1融合阳性，幽门螺杆菌感染阴性，并且对幽门螺杆菌根除治疗耐药（J Gastroenterol, 2004）。一项对胃MALT淋巴瘤的大规模分析显示，API2-MALT1融合阳性肿瘤对幽门螺杆菌根除治疗完全耐药。因此，我们将胃MALT淋巴瘤分为三组：(A)根除敏感，(B)根除抵抗，融合基因阴性，和(C)根除抵抗，融合基因阳性。每组表现出独特的临床病理特征（Am J外科病理，2004）。报告了一例API2-MALT1融合阴性的肺部MALT淋巴瘤病例，该病例发生在一名HIV阴性的年轻男性中（Leuk lymphoma, 2004）。少

AP12-MALT1 fusion gene is specific to mucosa-associated lymphoid tissue (MALT) lymphoma. We recently described a multiplex RT-PCR assay for this fission gene that can be applicable to paraffin sections. Using this assay, we clarified clinicopathological significances in MALT lymphomas of the lung, skin, ocular adnexa, colon, and stomach. The fusion gene was detected in 41% of pulmonary MALT lymphoma cases. The patients with fusion gene-positive tumors rarely had autoimmune disease, and their LDH level was often normal. Histologically the fusion-positive tumors were typical for MALT lymphoma, and were associated with nuclear BCL10 expression (Am J Pathol, 2003). Twenty-four Asian cases of cutaneous MALT lymphomas were negative for API2-MALT1 fusion and Borrelia infection. However, nuclear BCL10 expression, which is closely associated with the fusion gene, was frequently detected in the tumor calls, and was associated with macroscopically nodular lesion (Am J Surg Pathol, 2003). MALT lym … More phoma of the ocular adnexa showed the API2-MALT1 fusion in 13% of the cases analyzed. These positive cases often showed other chromosomal abnormalities, suggesting that some cases of the fusion-positive ocular MALT lymphoma might progress to high-grade lymphoma (Mod Pathol, 2003). MALT lymphoma of the colon showed the API2-MALT1 fusion in 15% of the cases analyzed. The fusion gene was often found in male patients, and was associated with advanced clinical stage. The latter observation suggests that a close follow-up may be needed for fusion-positive MALT lymphomas of the colon (Mod Pathol, 2003). An analysis of gastric MALT lymphomas involving multiple organs showed that these cases were frequently positive for API2-MALT1 fusion, negative for H. pylon infection, and resistant to H. pylori eradication therapy (J Gastroenterol, 2004). A large-scale analysis of gastric MALT lymphoma showed that API2-MALT1 fusion-positive tumors were totally resistant to H. pylori eradication therapy. Consequently, we divided gastric MALT lymphomas into three groups: (A) eradication-sensitive, (B) eradication-resistant, fusion gene-negative, and (C) eradication-resistant, fusion gene-positive. Each group showed unique clinicopathological features (Am J Surg Pathol, 2004). An API2-MALT1 fusion-negative pulmonary MALT lymphoma case which was developed in a HIV negative young man was reported (Leuk Lymphoma, 2004). Less