Mao E J, Oda D, Haigh W G, Beckmann A M
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Eur J Cancer B Oral Oncol. 1996 Jul;32B(4):260-3. doi: 10.1016/0964-1955(96)00008-5.
Recent evidence suggests that loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene plays a role in colorectal tumorigenesis and other cancers. However, little is known as to whether the APC gene contributes to the pathogenesis of oral squamous cell carcinoma. To assess involvement of both the APC gene and the human papillomavirus (HPV) in the development of oral pre-malignant and malignant lesions, we analysed DNA from 14 paired oral normal and pre-malignant or malignant paraffin-embedded biopsy specimens, and DNA from cultured normal and HPV 16-immortalised oral epithelial cells for the presence of LOH of APC and for HPV infection, using PCR based techniques. LOH of APC occurred in 80% of cases of oral epithelial dysplasia, 67% of carcinoma in situ, 50% of invasive squamous cell carcinoma cases, and in the HPV 16-immortalised oral epithelial cells. HPV was detected in half of the biopsy specimens, with HPV 16 as the dominant type. More than half of the carcinoma cases were found to contain both LOH of APC and HPV infection. These results suggest that LOH of APC is an early event during oral tumorigenesis. Our findings also suggest a strong correlation between HPV infection, particularly HPV 16, and LOH of the APC gene in oral squamous cell carcinomas.
最近的证据表明，腺瘤性息肉病（APC）基因的杂合性缺失（LOH）在结直肠癌发生及其他癌症中发挥作用。然而，关于APC基因是否参与口腔鳞状细胞癌的发病机制，目前所知甚少。为评估APC基因和人乳头瘤病毒（HPV）在口腔癌前病变和恶性病变发展中的作用，我们采用基于聚合酶链反应（PCR）的技术，分析了14对口腔正常组织与癌前或恶性石蜡包埋活检标本的DNA，以及培养的正常口腔上皮细胞和HPV 16永生化口腔上皮细胞的DNA，以检测APC基因的杂合性缺失及HPV感染情况。APC基因的杂合性缺失发生在80%的口腔上皮发育异常病例、67%的原位癌病例、50%的浸润性鳞状细胞癌病例以及HPV 16永生化口腔上皮细胞中。在一半的活检标本中检测到HPV，其中HPV 16为主要类型。超过一半的癌症病例被发现同时存在APC基因的杂合性缺失和HPV感染。这些结果表明，APC基因的杂合性缺失是口腔肿瘤发生过程中的早期事件。我们的研究结果还表明，HPV感染，尤其是HPV 16感染，与口腔鳞状细胞癌中APC基因的杂合性缺失之间存在密切关联。
