Department of Otolaryngology-Head and Neck Surgery.
Department of Radiology.
Otol Neurotol. 2018 Oct;39(9):1184-1190. doi: 10.1097/MAO.0000000000001935.
Stereotactic radiation therapy is increasingly used to treat vestibular schwannomas (VSs) primarily and to treat tumor remnants following microsurgery. Little data are available regarding the effects of radiation on VS cells. Tyrosine nitrosylation is a marker of oxidative stress following radiation in malignant tumors. It is not known how long irradiated tissue remains under oxidative stress, and if such modifications occur in benign neoplasms such as VSs treated with significantly lower doses of radiation. We immunostained sections from previously radiated VSs with an antibody that recognizes nitrosylated tyrosine residues to assess for ongoing oxidative stress.
Immunohistochemical analysis.
Four VSs, which recurred after excision, were treated with stereotactic radiation therapy. Ultimately each tumor required salvage reresection for regrowth. Histologic sections of each tumor before and after radiation were immunolabeled with a monoclonal antibody specific to nitrotyrosine and compared. Two VSs that underwent reresection of a growing tumor remnant without previous radiation therapy served as additional controls.
Irradiated tumors enlarged in volume by 3.16 to 8.62 mL following radiation. Preradiation sections demonstrated little to no nitrotyrosine immunostaining. Three of four of irradiated VSs demonstrated increased nitrotyrosine immunostaining in the postradiation sections compared with preradiation tumor sections. Nonirradiated VSs did not label with the antinitrotyrosine antibody.
VSs exhibit oxidative stress up to 7 years after radiotherapy, yet these VSs continued to enlarge. Thus, VSs that grow following radiation appear to possess mechanisms for cell survival and proliferation despite radiation-induced oxidative stress.
立体定向放射治疗越来越多地用于治疗前庭神经鞘瘤（VSs），主要是治疗显微手术后的肿瘤残余物。关于辐射对 VS 细胞的影响的数据很少。酪氨酸亚硝化为恶性肿瘤辐射后氧化应激的标志物。目前尚不清楚辐射组织在多长时间内处于氧化应激状态，如果这种修饰发生在良性肿瘤中，如接受低剂量辐射治疗的 VSs。我们用识别硝基酪氨酸残基的抗体对以前放射治疗的 VS 进行免疫染色，以评估持续的氧化应激。
免疫组织化学分析。
4 个 VS 切除后复发，接受立体定向放射治疗。最终，每个肿瘤都需要挽救性再切除以防止复发。每个肿瘤的组织学切片在放射治疗前后均用特异性硝基酪氨酸的单克隆抗体进行免疫标记，并进行比较。另外 2 个接受生长肿瘤残余物再切除的 VS，而没有以前的放射治疗，作为额外的对照。
放射治疗后，肿瘤体积从 3.16 至 8.62 毫升增大。放射前切片显示硝基酪氨酸免疫染色很少或没有。与放射前肿瘤切片相比，4 个放射治疗的 VS 中有 3 个在后放射治疗切片中显示出硝基酪氨酸免疫染色增加。未接受放射治疗的 VS 未与抗硝基酪氨酸抗体标记。
VSs 在放射治疗后长达 7 年内表现出氧化应激，但这些 VSs 仍在继续增大。因此，尽管存在辐射诱导的氧化应激，放射治疗后生长的 VS 似乎具有细胞存活和增殖的机制。
