The correlation between FHIT, P53 and MMR genes in human papillomavirus-associated cervical carcinoma.

BACKGROUND AND AIM: High risk human papillomavirus (HR-HPV) types have been closely associated with cervical carcinoma. However, other genetic events are likely to be required, in addition to HPV infection, for the development of cervical cancer. We investigated 20 human cervical carcinomas and 15 normal cervical tissues for the correlation between aberrant expression of the FHIT, p53 and MMR genes and their prognostic impact. METHODS AND RESULTS: The expression of p53, FHIT and MMR genes (hMSH2, hMLH1,GTBP/hMSH6,hPMS2, hPMS1) was assessed in relation to HPV infection by immunohistochemistry and PCR. HPV-16 and 18 DNA were detected in 95% and 25%, HPV m-RNA in 90% and 10% of cases; respectively. Homozygous deletion (HZD) and reduced FHIT protein was detected in 40% and 65% of cases, respectively; 25% of which showed abnormal gene transcripts. Reduced MMR gene expression was found in 19 cases. hMSH2 and hMLH1 showed the highest frequency (80% and 70%, respectively). p53 overexpression was present in 50% of cases with a single mutation in exon 7. There was a significant relation between FHIT aberrations, HPV-16 RNA, reduced hMLH-1 and hMSH- 2 expression; between reduced expression of hMSH-2 and p53 overexpression, GTPB-6, as well as between GTPB-6 and hMLH-1. Aberrant expression of p53, FHIT, hMLH1and GTPB-6 was significantly associated with recurrence. CONCLUSIONS: Aberrations involving MMR genes, FHIT and p53 are frequent in HPV-associated cervical carcinoma with a significant correlation between them. However, only the FHIT, p53, hMLH1 and GTPB6 aberrations could be used as predictors of tumor recurrences.

Role of human papilloma virus (HPV) in common and genital warts and its relation to P53 expression.

BACKGROUND AND AIM: Human papilloma viruses (HPVs) are small DNA tumor viruses that infect epithelial tissues and cause warts. One of the viral genes responsible for HPV's oncogenic activity is E6 which is known to inactivate the cellular p53 tumor suppressor gene. We aim to detect the presence of HPV infection and its different types in human warts, and to identify the relation between HPV and p53 expression in skin and genital lesions. PATIENTS AND METHODS: We studied markers of HPV infection in overall of 30 patients (20 with common warts, and 10 with genital warts). Also, 30 normal skin samples were taken from each patient as a normal control. Detection of HPV was done using polymerase chain reaction (PCR), and HPV typing was performed using LiPA (Line immuno Probe Assay). In addition, all skin lesions were examined by immunohistochemistry for p53 expression. RESULTS: In patients with common warts, HPV DNA was found in 4/20 (20%) of cases which was of HPV types 11, 31, 6, 33 (p=0.28). Also, P53 expression was found in 4/20 (20%) of cases (p=0.26). No single patient showed reactivity of both HPV and p53 expression. In patients with genital warts, however, HPV DNA was found in 6/10 (60%) of cases. Of these, 5 cases were positive for HPV type 6 and one case had HPV type 11. Three patients (30%) were positive for p53, and two of them (66%) were positive for both HPV and p53. In the normal skin control, 2/30 (6.6%) were positive for HPV DNA which were of types 5, and 31. CONCLUSIONS: We conclude that; (1) Prevalence rate of HPV infection in warts is higher than those of normal control group, and Egyptian patients with genital warts had higher prevalence rate of HPV than those with common warts, (2) In Egypt, HPV types 6, and 11 are the most prevalent genotypes associated with genital warts and HPV types 6, 11, 31, and 33 are associated with common warts, (3) There was no definite relation between p53 expression and HPV detection, (4) Also, there was no association between the different HPV types and p53 detection in these non-cancerous lesions.

p53 mutation in HCV-genotype-4 associated hepatocellular carcinoma in Egyptian patients.

HCV-associated hepatocellular carcinoma (HCC) is a common neoplasm in Egypt where genotype-4 is prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-genotype- 4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations/overexpression in relation to HCV-NS3 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-II and TRUGENE 5' NC' sequencing kit. Results were correlated to standard clinicopathologic prognostic factors for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation (13 mutations) by sequencing (72% concordance). The highest mutation rate was in exons 6 and 7 (30%) followed by exons 5 and 8 (20%). Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations were at codon 249 specific for AFB1 (AGG-->AGT, Arg-->Ser) and codon 248 specific for vinyl chloride contamination (CGG-->TGG, Arg-->Trp). Other mutations reported are novel. Immunostaining for HCV NS3 was detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-associated HCC and no significant relation between p53 mutations, HCV-NS3 expressions or any HCV sub-genotype-4 sequence.