Scheel Adam, Bellile Emily, McHugh Jonathan B, Walline Heather M, Prince Mark E, Urba Susan, Wolf Gregory T, Eisbruch Avraham, Worden Francis, Carey Thomas E, Bradford Carol
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan, U.S.A.
Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan, U.S.A.
Laryngoscope. 2016 Sep;126(9):E292-9. doi: 10.1002/lary.25915. Epub 2016 Jun 27.
OBJECTIVES/HYPOTHESIS: Assess tumor suppressor p53 (TP53) functional mutations in the context of other biomarkers in advanced larynx cancer.
Prospective analysis of pretreatment tumor TP53, human papillomavirus (HPV), Bcl-xL, and cyclin D1 status in stage III and IV larynx cancer patients in a clinical trial.
TP53 exons 4 through 9 from 58 tumors were sequenced. Mutations were grouped using three classifications based on their expected function. Each functional group was analyzed for response to induction chemotherapy, time to surgery, survival, HPV status, p16INK4a, Bcl-xl, and cyclin D1 expression.
TP53 mutations were found in 22 of 58 (37.9%) patients with advanced larynx cancer, including missense mutations in 13 of 58 (22.4%) patients, nonsense mutations in four of 58 (6.9%), and deletions in five of 58 (8.6%). High-risk HPV was found in 20 of 52 (38.5%) tumors. A classification based on Evolutionary Action score of p53 (EAp53) distinguished missense mutations with high risk for decreased survival from low-risk mutations (P = 0.0315). A model including this TP53 classification, HPV status, cyclin D1, and Bcl-xL staining significantly predicts survival (P = 0.0017).
EAp53 functional classification of TP53 mutants and biomarkers predict survival in advanced larynx cancer.
NA. Laryngoscope, 126:E292-E299, 2016.
目的/假设：在晚期喉癌的其他生物标志物背景下评估肿瘤抑制因子p53（TP53）的功能突变。
在一项临床试验中对III期和IV期喉癌患者的治疗前肿瘤TP53、人乳头瘤病毒（HPV）、Bcl-xL和细胞周期蛋白D1状态进行前瞻性分析。
对58个肿瘤的TP53外显子4至9进行测序。根据突变的预期功能，将突变分为三类。分析每个功能组对诱导化疗的反应、手术时间、生存率、HPV状态、p16INK4a、Bcl-xl和细胞周期蛋白D1表达。
58例（37.9%）晚期喉癌患者中发现22例TP53突变，其中58例（22.4%）患者为错义突变，58例（6.9%）患者为无义突变，58例（8.6%）患者为缺失突变。52个肿瘤中有20个（38.5%）检测到高危HPV。基于p53进化作用评分（EAp53）的分类法可区分出与低风险突变相比具有较高生存降低风险的错义突变（P = 0.0315）。一个包括此TP53分类、HPV状态、细胞周期蛋白D1和Bcl-xL染色的模型可显著预测生存率（P = 0.0017）。
TP53突变体的EAp53功能分类和生物标志物可预测晚期喉癌的生存率。
无。《喉镜》，2016年，第126卷，E292 - E299页
