Penhallow J, Steingrimsdottir H, Elamin F, Warnakulasuriya S, Farzaneh F, Johnson N, Tavassoli M
Oral Oncology Group, RCS Department of Dental Sciences, King's College School of Medicine and Dentistry, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, UK.
Int J Oncol. 1998 Jan;12(1):59-68. doi: 10.3892/ijo.12.1.59.
To examine the association between HPV infections and p53 gene aberrations, a panel of 28 oral squamous cell carcinomas (SCC) and 12 potentially malignant oral mucosal lesions were analysed for p53 mutations in exons 2-9. p53 protein was analysed by immunocytochemistry using DO7 antibody. The same panel was also examined for the possible presence of HPV infection. p53 overexpression was detected in 13/26 (50%) malignant and 2/9 (22%) premalignant lesions. Mutations in the coding region of the p53 gene were found in 10 malignant samples. None of the premalignant lesions were shown to have p53 mutations. The total number of p53 mutations in 10 samples were 14 of which 12 (85%) were in exon 5 suggesting the presence of hot spots in exon 5 for carcinogens involved in the transformation of oral epithelial cells. The presence of HPV DNA was first screened with consensus primers to the L1 region and nested PCR approach. HPV 6 and HPV 16 were detected in 14/28 (50%) oral SCC and 4 of 12 (33%) precancerous lesions, 7 tumours harboured both types. The samples were then examined for the presence of E6 oncogenic sequence of HPV16 using E6 specific primers. 7/27 (26%) SCC and 5/9 (55%) premalignant lesions harboured E6 DNA of which 6 (3 SCC and 3 premalignant) were negative with L1 primers suggesting possible integration of the specific viral genes or loss of other viral DNA sequences after integration of larger viral fragments. 9/10 (90%) SCC with p53 mutations were negative for E6 DNA. Our results show that both p53 alterations and HPV infection may be important etiological factors in the development of oral cancer. However, there is: i) No concordance between p53 mutations and its overexpression. ii) the presence of HPV capsid DNA (L1) does not necessarily indicate the presence of HPV oncogenic genes. iii) p53 gene mutations, but not overexpression, correlate with the absence of HPV 16-E6 and not L1 gene.
为了研究人乳头瘤病毒（HPV）感染与p53基因畸变之间的关联，对一组28例口腔鳞状细胞癌（SCC）和12例潜在恶性口腔黏膜病变进行了外显子2 - 9的p53突变分析。使用DO7抗体通过免疫细胞化学分析p53蛋白。对同一组样本还检测了是否存在HPV感染。在13/26（50%）的恶性病变和2/9（22%）的癌前病变中检测到p53过表达。在10个恶性样本中发现了p53基因编码区的突变。癌前病变均未显示有p53突变。10个样本中p53突变的总数为14个，其中12个（85%）在外显子5，这表明外显子5存在参与口腔上皮细胞转化的致癌物热点。首先用针对L1区域的共有引物和巢式PCR方法筛查HPV DNA的存在。在14/28（50%）的口腔SCC和12个癌前病变中的4个（33%）中检测到HPV 6和HPV 16，7个肿瘤同时含有这两种类型。然后使用E6特异性引物检测样本中HPV16的E6致癌序列的存在。7/27（26%）的SCC和5/9（55%）的癌前病变含有E6 DNA，其中6个（3个SCC和3个癌前病变）用L1引物检测为阴性，这表明特定病毒基因可能发生了整合，或者在较大病毒片段整合后其他病毒DNA序列丢失。9/10（90%）有p53突变的SCC的E6 DNA检测为阴性。我们的结果表明，p53改变和HPV感染可能都是口腔癌发生的重要病因。然而，存在以下情况：i）p53突变与其过表达之间没有一致性。ii）HPV衣壳DNA（L1）的存在不一定表明存在HPV致癌基因。iii）p53基因突变而非过表达与HPV 16 - E6而非L1基因的缺失相关。
