Astori G, Merluzzi S, Arzese A, Brosolo P, de Pretis G, Maieron R, Pipan C, Botta G A
Institute of Microbiology, Medical Faculty, University of Udine, Udine, Italy.
Digestion. 2001;64(1):9-14. doi: 10.1159/000048834.
BACKGROUND/AIM: There is evidence of a possible etiological role of human papillomaviruses (HPVs) in the development of esophageal tumors. Loss of function of the wild-type p53 tumor suppressor gene product by binding to E6 oncoproteins of high-risk HPVs is considered an important event in tumor development. The aim of this study was to verify the prevalence of HPV infection and p53 mutation in esophageal tumor tissue samples and in the adjacent normal mucosa in patients from a high-risk area in Italy.
DNA from 33 biopsy specimens (17 tumor sample biopsies and 16 samples of adjacent normal mucosa) was screened for HPV DNA using two polymerase chain reaction based procedures. Restriction fragment length polymorphism analysis was used for typing. Screening of p53 mutations was performed with polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing.
Overall, 8 of 17 patients presented HPV DNA; HPV 16 was detected in 4 of 8 samples. Samples from tumors and adjacent mucosa were positive for mucosal HPVs in 7 of 17 and 4 of 16 cases, respectively. In 1 case, HPV DNA was detected in the normal mucosa only. None of the samples contained HPVs of the epidermodysplasia verruciformis or cutaneous groups. Mutations of p53 were detected in two HPV DNA negative samples. In both cases, the mutation was present in the tumor only.
Our results are in favor of the involvement of both aberrant p53 expression and HPV infection in the development of esophageal tumors. The high HPV infection rate in patients from a high-risk region suggests that subjects harboring HPVs (in particular HPV 16) in the esophagus should be considered at risk of esophageal malignancies.
背景/目的：有证据表明人乳头瘤病毒（HPV）在食管肿瘤的发生中可能具有病因学作用。野生型p53肿瘤抑制基因产物通过与高危型HPV的E6癌蛋白结合而丧失功能被认为是肿瘤发生中的一个重要事件。本研究的目的是验证意大利高危地区患者食管肿瘤组织样本及相邻正常黏膜中HPV感染和p53突变的发生率。
采用两种基于聚合酶链反应的方法对33份活检标本（17份肿瘤样本活检和16份相邻正常黏膜样本）的DNA进行HPV DNA筛查。采用限制性片段长度多态性分析进行分型。用聚合酶链反应-单链构象多态性分析和DNA测序进行p53突变筛查。
总体而言，17例患者中有8例存在HPV DNA；8份样本中的4份检测到HPV 16。肿瘤样本和相邻黏膜样本中，分别有17例中的7例和16例中的4例黏膜HPV呈阳性。1例仅在正常黏膜中检测到HPV DNA。所有样本均未含有疣状表皮发育不良型或皮肤型HPV。在两份HPV DNA阴性样本中检测到p53突变。在这两例中，突变仅存在于肿瘤中。
我们的结果支持异常p53表达和HPV感染均参与食管肿瘤的发生。高危地区患者的高HPV感染率表明，食管中携带HPV（尤其是HPV 16）的个体应被视为有患食管恶性肿瘤的风险。
