Chang F, Syrjänen S, Wang L, Shen Q, Syrjänen K
Department of Pathology, University of Kuopio, Finland.
Anticancer Res. 1997 Jan-Feb;17(1B):709-15.
Oesophageal epithelium is frequently exposed to various carcinogens and mutagens, many of which may cause p53 gene mutations. The epithelium can also be infected with human papillomavirus (HPV), the E6 protein of which may complex with p53 protein and facilitate its degradation. To identify HPV infection and p53 overexpression in oesophageal cancer, we performed immunohistochemical analysis using CM-1 anti-p53 antibody and DNA in situ hybridization with biotinylated HPV DNA probes on paraffin-embedded sections in 36 patients with oesophageal squamous cell carcinomas derived from a high-incidence area in northern China. Samples from cancer tissue, adjacent epithelia, regional lymph nodes as well as resection margins were examined. p53 protein accumulation was detected in 55.6% (20/36) of cancer samples, in 20% (1/5) of hyperplastic epithelium, in 20% (2/10) of dysplastic lesions as well as in 67% (2/3) of carcinoma in situ lesions adjacent to invasive carcinomas. HPV DNA sequences were demonstrated in 3 patients (8.3% of the total). Two of these HPV-positive carcinomas were immunohistochemically negative for p53 and one was weakly positive. Our results suggest that p53 overexpression is frequently found in oesophageal carcinomas and that p53 alteration may be an early event in esophageal carcinogenesis. HPV and elevated p53 are not mutually exclusive events, instead they can coexist in some oesophageal squamous cell carcinomas.
食管上皮经常暴露于各种致癌物和诱变剂中,其中许多可能导致p53基因突变。该上皮还可能感染人乳头瘤病毒(HPV),其E6蛋白可能与p53蛋白结合并促进其降解。为了鉴定食管癌中的HPV感染和p53过表达,我们使用CM-1抗p53抗体进行免疫组织化学分析,并对来自中国北方高发地区的36例食管鳞状细胞癌石蜡包埋切片进行生物素化HPV DNA探针原位杂交。检查了癌组织、相邻上皮、区域淋巴结以及手术切缘的样本。在55.6%(20/36)的癌样本、20%(1/5)的增生上皮、20%(2/10)的发育异常病变以及67%(2/3)的与浸润癌相邻的原位癌病变中检测到p53蛋白积聚。在3例患者(占总数的8.3%)中检测到HPV DNA序列。其中2例HPV阳性癌免疫组织化学检测p53为阴性,1例为弱阳性。我们的结果表明,p53过表达在食管癌中经常发现,并且p53改变可能是食管癌发生的早期事件。HPV和p53升高并非相互排斥的事件,相反,它们可以在一些食管鳞状细胞癌中共存。