ABSTRACT
Cervical cancer is caused by persistent infections through high risk (HR) types of human HPVs, particularly HPV 16 and 18. HR-HPV types encode two potent oncogenes, referred to as E6 and E7. Both are required to induce and maintain neoplastic growth of cervical cancer cells. Cyclin dependent kinase inhibitor genes as for example p16INK4A were shown to be negative regulated by active pRb. Inactivation of pRb by E7 thus releases the p16 gene from its negative transcriptional control and results in significant overexpression of p16 encoded protein in HPV transformed cells. It has been demonstrated that p16 protein can be detected in cervical preneoplasia all high grade SIL or invasive cancers, whereas no expression was detected in normal, metaplastic or inflammatory cervical lesions. Moreover, low grade cervical lesions induced by low risk HPV infection but histological indistinguishable from low grade lesions induced by HR-HPV-infections could be clearly differentiated by p16INK4A immunohistochemistry, showing negative staining for p16 protein. The objective of this study is to examine the expression of p16 protein in cervical carcinoma in Thailand. Immunohistochemical analysis of p16INK4A was performed on 53 formalin fixed and paraffin embedded samples of various stages of cervical neoplastic lesions. There are squamous cell carcinoma in situ 8 cases, squamous cell carcinoma in situ with glandular involvement 16 cases, microinvasive squamous cell carcinoma 13 cases and invasive squamous cell carcinoma 16 cases. The specimens were taken from cervical biopsy, cervical conization and hysterectomy in the year 2000 at National Cancer Institute. Strong immunoreactivity for the p16 protein was observed in only the nuclei and cytoplasm of all cervical neoplastic cells. This study supported the idea that immunohistochemical overexpression of the p16 protein may be a useful screening test for cervical cancer. In addition, p16 immunohistochemistry is useful for helping in the interpretation of cervical histology samples, facilitating more rapid diagnosis.
ABSTRACT
Cytochrome P450 2E1 and GSTM1 play major roles in metabolic activation and detoxification of many carcinogens and polymorphisms in the encoding genes have been reported to be individually associated with increased susceptibility to certain cancer. In the present study, we investigated the RsaI, PstI and DraI polymorphisms of the CYP2E1 gene and the null GSTM1 genotype in a Thai population. DNA samples from 485 individuals were analysed by polymerase chain reaction with restriction fragment length (PCR/RFLP). The frequency of RsaI and PstI predominant homozygous alleles (c1/c1) was 73.2%, heterozygous allele (c1/c2) was 25.6% and rare homozygous allele (c2/c2) was 1.2%. For the DraI polymorphism, the frequency of the predominant allele (DD) was 59.6%, heterozygous (CD) was 40% and rare allele (CC) was 0.4%. The frequency of GSTM1 null genotype was 62.7%. The distribution and frequencies of these alleles showed different pattern from those found in Caucasian and some other Asian populations. With the large population in this study, we believed that our results are reliable estimates of the frequencies of the polymorphic CYP2E1 and GSTM1 alleles in Thai population and should provide a base for further epidemiological studies on their links with cancer development.