Ireland A P, Shibata D K, Chandrasoma P, Lord R V, Peters J H, DeMeester T R
Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033-4612, USA.
Ann Surg. 2000 Feb;231(2):179-87. doi: 10.1097/00000658-200002000-00005.
To compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers.
The p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level.
DNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n = 19), cardia (esophagogastric junction, n = 12), or subcardia (n = 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with single-strand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor.
p53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar.
Adenocarcinomas of the esophagus and cardia have a similar frequency and spectrum of p53 gene mutations, suggesting that these tumors have a common pathogenesis. Patients with mutations are younger, have signs of more advanced disease, and have a poorer prognosis than patients without mutations.
比较食管腺癌和贲门腺癌中p53基因突变的频率和谱，并比较p53基因发生突变和未发生突变的癌症患者的临床及病理特征。
p53基因在人类癌症中常发生突变，据报道超过50%的食管腺癌存在p53基因突变。尽管许多研究调查了食管腺癌或食管胃交界腺癌中p53蛋白过表达的频率，但很少有研究评估这些肿瘤中p53基因突变的频率及临床意义。特别是，p53基因突变的预后重要性尚不确定。食管腺癌和贲门腺癌具有许多流行病学和病理学特征，但它们是否代表同一肿瘤仍存在争议。比较食管腺癌和贲门腺癌中突变的频率和谱将检验这些肿瘤在分子水平上是否也相似。
从因食管腺癌（n = 19）、贲门癌（食管胃交界，n = 12）或贲门下方癌（n = 6）接受食管胃切除术的患者经显微切割的石蜡包埋肿瘤组织中提取DNA。使用聚合酶链反应-单链构象多态性及对显示异常迁移的条带进行DNA测序分析p53基因的第5至8外显子是否存在突变。通过突变特异性寡核苷酸与从肿瘤中分离的DNA进行选择性杂交来确认突变的存在。
在37例肿瘤中有18例（48.6%）检测到p53基因突变。p53基因发生突变的肿瘤患者明显更年轻，预后明显更差。食管腺癌（53%）和贲门腺癌（58%）中p53基因突变的发生率相似。相比之下，贲门下方腺癌中突变相对少见（1例突变肿瘤[17%]）。在食管癌和贲门癌中发现的突变类型也相似。
食管腺癌和贲门腺癌中p53基因突变的频率和谱相似，提示这些肿瘤具有共同的发病机制。与未发生突变的患者相比，发生突变的患者更年轻，有疾病进展更晚期的迹象，预后更差。
