D.N. Dokianakis

p53 codon 72 polymorphism and its association with bladder cancer.

p53 codon 72 Arg homozygosity has been associated with increased risk of developing cervical cancer. This association has been tested in various human cancers with controversial results. In the present study we investigated the impact of this polymorphism in a population-based case-control study of bladder cancer. Using allele-specific polymerase chain reaction to detect the p53 codon 72 polymorphism, we tested peripheral blood samples from 50 patients with bladder cancer and 99 healthy individuals of similar age and from the same geographical region. Tumor specimens from all bladder cancer patients were examined for the presence of human papilloma virus (HPV). The distribution of p53 alleles in bladder cancer patients and in controls was statistically significant (P<0.002; odds ratio, 2.67; 95% confidence interval, 1.38-5.20), and homozygosity for arginine at residue 72 was associated with an increased risk for bladder cancer (P<0.00002; odds ratio, 4.69; 95% confidence interval, 2.13-10.41). The presence of HPV was found in six of the 50 patients (12%). This is the first study correlating p53 codon 72 polymorphism with bladder cancer. Our results provide evidence that this p53 polymorphism is implicated in bladder carcinogenesis and that individuals harboring the Arg/Arg genotype have an increased risk of developing bladder cancer.

Human papillomavirus infection of non-melanoma skin cancers in immunocompetent hosts

Human papilloma viruses (HPVs) consist of more than 70 different types and are known to be associated with numerous malignant tumors, including carcinomas of the mucosal and cutaneous epithelium. Non-melanoma skin carcinoma (NMSC) is the most frequently occurring malignancy worldwide in the Caucasian population. Most studies examining the involvement of papillomaviruses in the development of cutaneous carcinomas have been performed on lesions from patients with epidermodysplasia verruciformis or from immunosuppressed patients. Our specimens were obtained from 108 immunocompetent patients with benign and malignant skin lesions, and HPVs were detected in 27%. HPV 8 and HPV 18 were the most frequent types (62 and 48%, respectively). Our results suggest that HPVs, particularly the oncogenic potential of certain types such as HPV 8, 18, and 5 could contribute to the development of NMSCs.

Molecular Basis of Gynecological Cancer

Abstract: Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Genes that cause cancer are of two distinct types: oncogenes and onco‐suppressor genes. The normal proto‐oncogene can be converted into an active oncogene by deletion or point mutation in its coding sequence, gene amplification, and by specific chromosome rearrangements. Mutations and abnormal expression in ras, myc, c‐erbB‐2, and other oncogenes have been reported in several types of gynecological cancer. Onco‐suppressor genes are involved in gynecological cancer, their functions are localized in different phases of the cell cycle. Structural changes and deletions of these genes can cause cancer. Mutations in the p53, BRCA1, DCC, and PTEN genes have been reported in gynecological cancers such as ovarian, cervical, and endometrial cancer. Human papillomaviruses are of major interest because specific types (HPV‐16, ‐18, and several others) have been identified as causative agents in at least 90% of cancers of the cervix. In this study we summarize the available information regarding the implication of specific oncogenes, onco‐suppressor genes, and HPV in the development of female genital malignancies.

In vivo detection of human papilloma virus-induced lesions of anogenital area after application of acetic acid: a novel and accurate approach to a trivial method.

Human papilloma virus infection is increasing at an alarming rate. The ability of the virus to establish a subclinical infection and its association with malignancy of the lower genital tract make the statistics even more worrisome. Topical application of acetic acid solution provokes temporal alterations of the light-scattering properties of human papilloma virus-induced lesions of anogenital area. For the in vivo study of the phenomenon, an imaging system has been employed, which performs time-lapse imaging and enables the calculation and display of the kinetics of the provoked alterations in any point within the examined area. Confirmation of diagnosis has been established with conventional histology and polymerase chain reaction. It has been shown that the method provides early detection and staging of skin alteration or transformation due to human papilloma virus infection and enables mapping of the infected area.

Ras gene activation in malignant cells of human ovarian carcinoma peritoneal fluids.

In this study, we showed, for the first time, the pattern of point mutations at codon 12 of the K-ras, H-ras and N-ras genes, using polymerase chain reaction and restriction fragment length polymorphism analysis in 47 malignant cytologic specimens of ovarian adenocarcinoma peritoneal fluids. Forty-seven % of the samples were found to carry a point mutation at codon 12 of K-ras gene. Also, 21 cystadenoma peritoneal fluids were used as control specimens for the detection of ras mutations. Fourteen % of these samples were found to carry a point mutation at codon 12 of the K-ras gene. The prevalence of K-ras gene mutations were statistically correlated with FIGO and surgical stage of the malignant specimens. Our data demonstrates that the K-ras gene mutations are mainly affected (47%) in the malignant cells of the peritoneal washings or ascites of women with ovarian adenocarcinomas and may have value for the early diagnosis and monitoring of these neoplasms.