Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Acta Histochem Cytochem. 2011 Jun 29;44(3):119-31. doi: 10.1267/ahc.10024. Epub 2011 Jun 3.
This study investigated autophagy in 37 cases of nasopharyngeal lymphomas including 23 nasal natural killer (NK)/T-cell lymphomas (NKTCL), 3 cytotoxic T-cell lymphomas (cytotoxic-TML) and 9 B-cell lymphomas (BML) by means of antigen-retrieval immunohistochemistry of beclin-1, LC3, mitochondria (AE-1) and cathepsin D. Peculiar necrosis was noted in EBV(+) lymphomas comprising 21 NKTCL, 2 cytotoxic-TML and 1 BML. Lymphomas without peculiar necrosis showed high expression of beclin-1, macrogranular cytoplasmal stain of LC3 with sporadic nuclear stain, a hallmark of autophagic cell death (ACD), some aggregated mitochondria and high expression of cathepsin D, suggesting a state of growth with enhanced autophagy with sporadic ACD. EBV(+) NKTCL with the peculiar necrosis, showed significantly low level of macrogranular staining of LC3, aggregated mitochondria and low expression of cathepsin D in the cellular areas when degenerative lymphoma cells showed decreased beclin-1, significantly advanced LC3-labeled autophagy, residual aggregated mitochondria and significantly reduced expression of cathepsin D, suggesting advanced autophagy with regional ACD. Consequently it was suggested that enhanced autophagy and reduced expression of lysosomal enzymes induced regional ACD under EBV infection in NKTCL.
本研究通过抗原修复免疫组化法检测了 beclin-1、LC3、线粒体（AE-1）和组织蛋白酶 D 在 37 例鼻咽部淋巴瘤中的自噬情况，包括 23 例鼻型自然杀伤（NK）/T 细胞淋巴瘤（NKTCL）、3 例细胞毒性 T 细胞淋巴瘤（cytotoxic-TML）和 9 例 B 细胞淋巴瘤（BML）。在包含 21 例 NKTCL、2 例细胞毒性-TML 和 1 例 BML 的 EBV(+)淋巴瘤中观察到特殊坏死。无特殊坏死的淋巴瘤中，beclin-1 表达较高，LC3 呈大颗粒细胞质染色，核散在染色，提示自噬性细胞死亡（ACD），线粒体聚集，组织蛋白酶 D 表达较高，提示存在生长增强和散在 ACD 的自噬状态。具有特殊坏死的 EBV(+)NKTCL，在退行性淋巴瘤细胞 beclin-1 减少时，LC3 的大颗粒染色、聚集的线粒体和组织蛋白酶 D 的表达明显降低，表明在 EBV 感染的 NKTCL 中，晚期自噬伴有局部 ACD。因此，推测 EBV 感染可诱导 NKTCL 中增强的自噬和溶酶体酶表达降低，导致局部 ACD。
