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The Related Factors Of Vulvar Carcinogenesis

Posted on:2002-05-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:X WuFull Text:PDF
GTID:1104360092995884Subject:Oncology
Abstract/Summary:PDF Full Text Request
IntroductionThe vulva is a unique anatomical site at which human papilloma virus ( HPV) infection often occurs, as in the case of vulvar condyloma acuminatum ( VGA). In recent years, HPV DNA has been detected in vulvar intraepithelial neoplasia (VIN) at rates varying from about 59 to 90% , and in vulvar squa-mous cell carcinoma ( VSCC) at rates ranging from 10 to 60% . The carcinogenic role of HPV in these epithelial lesions has also been studied. Updated research has shown that certain HPV products can bind and inactivate p53 protein , a tumor suppressor gene product, thus leading to the transformation of epithelial cells. It is therefore of interest to study the relationship between some oncogene expression and HPV infection.Carcinogenesis in vulva is a multistep process. Histologically this is supported by the transition over time from normal epithelium to hyperplasia to dysplasia to squamous cell carcinoma in situ and finally to invasive squamous cell carcinoma. Underlying this histologic transition are multiple molecular and cellular changes. It maybe include changes in the expression of growth factor/receptor genes and oncogene. Therefore we selected MUC1, MK, p53 , Bel -2 oncogene protein and EGF family system to study the relationship between oncogene expre-sion and HPV infection.Mucin 1 (MUC1) is a high molecular weight transmembrane glycoprotein. High levels of MUC1 expression are associated with a poor prognosis of malignant tumor, such as cancers of the breast, ovary, pancreas, prostate, stomach and colon, esophagus, pharynx, larynx, eyelid and oral mucosa.Midkine (MK) is a novel heparin binding growth/differentiation factor. High levels of MK expression were observed in some types of human malignan-cies, such as Wilms' tumors, neuroblastoma, hepatocellular carcinoma and some tumors of the breast, brain, lung, and gastrointestinal tract, prostate, colorec-tal, ovarian tumors, bladder cancer and esophageal cancer, glioblastomas. In neuroblastomas, glioblastomas and bladder cancer, high levels of MK expression are correlated with poor prognosis.Epidermal growth factor ( EGF) family members ( TGF-a, EGF) and its receptor Epidermal growth factor receptor ( EGFR) are thought to play an important role in the development of multiple human tumors, such as cancers of skin, cervix, esophagus, laryngeal, head and neck, EGFR over - expression correlates with a poor prognosis in cancers of cervix and vulva.P53 protein is a tumor suppressor gene product and bcl - 2 protein is a anti - apoptotic oncogene product, they play an important role in the development of multiple human tumors.However, little is known about the differences in these oncogene and growth factors expression among normal, benign, and malignant vulvar tissues, it remains unknown whether they plays a role in either an early stage of carcinogene-sis or a later stage.In the present study, we attempted to clarify the role of these oncogene in carcinogenesis through examination of their expressions in a spectrum of vulvar lesions ranging from benign VGA through premalignant VIN to malignant VSCC conditions, and to assess whether their elevated expressions are associated with malignant transformation of vulvar squamous cells, as well as to analyze the relationship between these oncogene expression and HPV infection.MethodsThirty vulvar squamous cell carcinomas ( VSCC) , Fifteen vulvar intraepi-thelial neoplasia (VIN) , Ten vulvar condyloma acuminata ( VGA) were studied. 1. Polymerase chain reaction (PCR) was employed to detect the presence or absence of HPV in these diseased skin. 2. Oncogene protein expressions were examined by streptavidin - biotin - immunoperoxidase method. 3. Oncogeneprotein expressions were compared with clinicalpathologic features of vulvar tumors including HPV infection.Results and conclution1. HPV DNA detectionResult: 86.7% (13/15) of patients with VSCC were HPV - negative, 13. 3% (2/15) with VSCC were HPV6,11 positive and 20% (1/5) with VINIII were HPV16,18 positive, w...
Keywords/Search Tags:Human papillomavirus, Mucinl, Midkine, Epidermal growth factor, Vulvar tumors
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