8-hydroxy-2--deoxyguanosine and Vulvar-Neoplasms

Vulvar cancer represents an important medical problem worldwide whose incidence is increasing at an alarming rate in young females. Several factors have been linked to vulvar cancer development, but its exact pathogenesis remains to be determined. Vulvar tumorigenesis proceeds through intermediate dysplastic lesions, known as vulvar intraepithelial neoplasias, frequently associated with non-neoplastic epithelial disorders of the vulva, such as lichen sclerosus and squamous cell hyperplasia. In this study, the expression of the CDK inhibitor p27Kip1 and the extent of endogenous oxidative DNA damage were evaluated in vulvar specimens, including normal tissues, lichen sclerosus, squamous cell hyperplasia, vulvar intraepithelial neoplasias and invasive squamous cell carcinomas. We found that p27Kip1 was constantly expressed in normal vulvar epithelium cells while a progressive significant reduction in the percentage of p27Kip1-positive cells was observed in vulvar intraepithelial neoplasias (77%) and in invasive carcinomas (64%). Mean percentage of positive cells in invasive carcinomas, but not in vulvar intraepithelial neoplasias, was also significantly lower than squamous cell hyperplasia lesions (78%) while lichen sclerosus displayed a percentage of positive cells (45%) significantly lower than both vulvar intraepithelial neoplasias and invasive carcinomas. 8-hydroxydeoxyguanosine (8-OHdG) is considered a sensitive biomarker for oxidative stress. We observed a progressive significant increase in the levels of 8-OHdG and in the percentage of positive cells from normal vulvar epithelium to vulvar intraepithelial neoplasias (25%) and to invasive carcinomas (64%). Squamous cell hyperplasia displayed an intermediate percentage of positive cells comparable to vulvar intraepithelial neoplasias 2 but significantly higher than vulvar intraepithelial neoplasias 1 and lower than invasive carcinomas. Lichen sclerosus staining was significantly lower than carcinomas but higher than vulvar intraepithelial neoplasias and squamous cell hyperplasia. These results demonstrate that expression of p27Kip1 is downregulated while oxidative DNA damage increases from early non-neoplastic epithelial alterations through vulvar intraepithelial neoplasias to invasive vulvar carcinomas. Thus, both parameters might play an important role in the development of this cancer and their study might contribute to our understanding of human vulvar carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p27; Deoxyguanosine; DNA Damage; Female; Humans; Hyperplasia; Immunohistochemistry; Lichen Sclerosus et Atrophicus; Middle Aged; Oxidative Stress; Vulva; Vulvar Neoplasms

To detect the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) which is an oxygen-radical-forming agent, in the urine of patients with (n = 18) or without (n = 10) carcinoma of the female genitalia. None of the patients had been receiving any treatment before their urinary 8-OHdG levels were measured.. Urinary 8-OHdG was extracted by a solid-phase technique, and its level was determined by high-performance liquid chromatography (HPLC) with an electric chemical detector (ECD).. We determined that the urinary 8-OHdG level decreased with as the age of the patient increased, and was extremely high in advanced cancer and recurrent cancer in a considerable number of patients. The urinary 8-OHdG level (1,827 +/- 1,500 pmol/kg/day, mean +/- SEM) in 18 patients with carcinoma was significantly higher (p < or = 0.05) than that (747 +/- 425 pmol/kg/day) in 10 patients without carcinoma.. These results suggest that it might be possible to determine the spread of cancer to some extent by determining a patient's urinary 8-OHdG level.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aging; Chromatography, High Pressure Liquid; Deoxyguanosine; Female; Genital Neoplasms, Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms