Melling Nathaniel, Norrenbrock Sonja, Kluth Martina, Simon Ronald, Hube-Magg Claudia, Steurer Stefan, Hinsch Andrea, Burandt Eike, Jacobsen Frank, Wilczak Waldemar, Quaas Alexander, Bockhorn Maximillian, Grupp Katharina, Tachezy Michael, Izbicki Jakob, Sauter Guido, Gebauer Florian
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
Institute for Pathology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
Oncol Lett. 2019 Apr;17(4):3826-3834. doi: 10.3892/ol.2019.10020. Epub 2019 Feb 6.
Immunohistochemistry studies on p53 inactivation in esophageal cancer are available with inconclusive results. Data on the combined effect of p53 protein accumulation and genomic deactivation in large scale studies for esophageal cancer are currently lacking. A tissue microarray with 691 esophageal cancer samples was analyzed by p53 immunohistochemistry and fluorescence hybridization (FISH). Nuclear p53 accumulation was observed in 45.9% of patients with adenocarcinoma (AC) and in 40.0% in squamous cell carcinoma (SCC). Heterozygous deletions occurred in 40.9% in AC and in 19.4% in SCC. Homozygous deletions did not occur at all. High-level p53 immunostaining was associated with shortened overall survival in AC and SCC while deletions alone showed no correlation with survival. High-level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006). Associations between p53 immunostaining and SCC were not found. deletions were found to be associated with advanced tumor stages (P=0.028) and the presence of lymph node metastasis (P=0.009) in SCC. In conclusion, strong p53 immunostaining, but not deletion alone, is associated with unfavorable outcomes and may therefore represent a clinically useful molecular marker in esophageal cancer.
关于食管癌中p53失活的免疫组织化学研究结果尚无定论。目前缺乏大规模食管癌研究中p53蛋白积累和基因组失活联合效应的数据。采用p53免疫组织化学和荧光杂交（FISH）分析了一个包含691例食管癌样本的组织芯片。在45.9%的腺癌（AC）患者和40.0%的鳞状细胞癌（SCC）患者中观察到核p53积累。AC中杂合缺失发生率为40.9%，SCC中为19.4%。未发现纯合缺失。AC和SCC中，高水平p53免疫染色与总生存期缩短相关，而单纯缺失与生存期无相关性。AC患者中高水平p53免疫染色与肿瘤进展（P=0.019）、国际癌症控制联盟分期（P=0.004）、分级（P=0.027）及切缘状态（P=0.006）相关。未发现p53免疫染色与SCC之间存在关联。在SCC中，缺失与肿瘤进展期（P=0.028）及淋巴结转移（P=0.009）相关。总之，强烈的p53免疫染色而非单纯缺失与不良预后相关，因此可能是食管癌中一种具有临床应用价值的分子标志物。
