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Vulvar squamous cell carcinoma : genetics, morphology and clinical behaviour
Vulvar squamous cell carcinoma (VSCC) has two etiological pathways: a high risk human papillomavirus (HPV)-dependent route, which has usual vulvar intraepithelial neoplasia (uVIN) as a precursor lesion, and an HPV-independent route, which is associated with differentiated VIN (dVIN), lichen sclerosus, and genetic alterations, such as TP53 mutations.
Although most cases of early stage vulvar cancer have a good prognosis, recurrence and rapid tumour progression can oc¬cur.
The etiology of HPV positive vulvar cancer is quite well understood, but the HPV in-dependent axis remains to be unravelled. This thesis aims to gain knowledge on the origin of this type of vulvar cancer through the study of two mechanisms: genetic and morphological alterations in vulvar cancer.
An overview of the literature on genetic and...Show more
Vulvar cancer is a relatively rare gynaecologic malignancy with an annual incidence in developed countries of approximately 2 per 100,000 women.
Vulvar squamous cell carcinoma (VSCC) has two etiological pathways: a high risk human papillomavirus (HPV)-dependent route, which has usual vulvar intraepithelial neoplasia (uVIN) as a precursor lesion, and an HPV-independent route, which is associated with differentiated VIN (dVIN), lichen sclerosus, and genetic alterations, such as TP53 mutations.
Although most cases of early stage vulvar cancer have a good prognosis, recurrence and rapid tumour progression can oc¬cur.
The etiology of HPV positive vulvar cancer is quite well understood, but the HPV in-dependent axis remains to be unravelled. This thesis aims to gain knowledge on the origin of this type of vulvar cancer through the study of two mechanisms: genetic and morphological alterations in vulvar cancer.
An overview of the literature on genetic and epigenetic changes in vulvar cancer was made. We designed a mass spectrometry based mutation panel and investigated the prevalence of somatic mutations in a cohort of vulvar cancer patients. Also, markers of Epithelial-to-Mesenchimal-Transition such as spindle cell morphology and L1CAM-expression were studied in a large group of patients. These results were related to a worse survival.
https://www.gildeprint.nl/flippingbook/4336-vulvar-squamous-cell-carcinoma/
Show less- All authors
- Trietsch, M.D.
- Supervisor
- Peters, A.A.W.; Fleuren, G.J.M.
- Co-supervisor
- Gaarenstroom, K.N.
- Committee
- Vijver, M.J. van de; Jordanova, E.S.; Trimbos, J.B.M.Z.; Smit, V.T.H.B.M.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Medicine, Leiden University Medical Center (LUMC) , Leiden University
- Date
- 2017-11-09
- ISBN (print)
- 9789462337695
Funding
- Sponsorship
- Financial support for the printing of this thesis was provided by: Leiden University, the departments of gynaecology and pathology of the Leiden University Medical Center, Nederlandse Vereniging voor Obstetrie en Gynaecologie, Stichting Olijf, Nederlandse Vereniging voor Vulvapathologie, Novogene, 3D Histech – Sysmex, Chipsoft BV