Trask Douglas K, Wolf Gregory T, Bradford Carol R, Fisher Susan G, Devaney Kenneth, Johnson Mark, Singleton Timothy, Wicha Max
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, USA.
Laryngoscope. 2002 Apr;112(4):638-44. doi: 10.1097/00005537-200204000-00009.
OBJECTIVES/HYPOTHESIS: Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy.
Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome.
To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival.
The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation.
The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.
目的/假设：晚期喉癌的诱导化疗和根治性放射治疗已被证明能达到与全喉切除术及术后放射治疗相似的生存率。对于晚期喉癌患者，保留喉部的治疗方案可显著提高生活质量。然而，哪些患者对器官保留方案反应最佳仍不清楚。Bcl-2家族蛋白参与细胞凋亡的调控，并可能影响肿瘤对化疗的反应。
对免疫组化肿瘤特征和临床结果进行回顾性分析。
为确定Bcl-2家族蛋白是否可预测器官保留的成功，对美国退伍军人事务部合作研究项目（VA CSP-268）中47例晚期喉癌患者的组织标本进行免疫组化分析，评估Bcl-2、Bcl-X(L)和Bax蛋白的表达。诱导化疗后，肿瘤反应分为完全缓解或部分缓解/无反应。蛋白表达与肿瘤反应、器官保留及患者总生存率相关。
仅15%的标本中Bcl-2蛋白高表达，但7例Bcl-2高表达的肿瘤中有5例显示完全缓解（P = 0.10）。大多数肿瘤Bcl-X(L)高表达（74%）。Bcl-X(L)表达降低与完全缓解（P = 0.143）及喉部保留（P = 0.06）相关。大多数患者（81%）Bax表达水平升高。Bax表达降低与完全缓解率相关（P = 0.074），但Bax表达与喉部保留无相关性。
研究结果表明，喉癌细胞通常仅高水平产生一种凋亡保护蛋白，即Bcl-2或Bcl-X(L)。正在进行更多患者的前瞻性研究，以确定Bcl-X(L)表达是否将成为预测喉部保留的有用标志物。
