Cover Page
The handle http://hdl.handle.net/1887/54945 holds various files of this Leiden University dissertation.
Author: Trietsch, M.D.
Title: Vulvar squamous cell carcinoma : genetics, morphology and clinical behaviour
Issue Date: 2017-11-09
Marjolijn Dorothea Trietsch
Vulvar squamous cell carcinoma
Genetics, morphology and clinical behaviour
Vulvar squamous cell carcinoma
Genetics, morphology and clinical behaviour
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op donderdag 9 november 2017
klokke 16.15 door
Marjolijn Dorothea Trietsch
Geboren te ’s Gravenhage
in 1983
Promotiecommissie
Promotores:
Prof. dr. A.A.W. Peters Prof. dr. G.J.M. Fleuren
Copromotor
:Dr. K.N. Gaarenstroom
Overige Leden:
Prof. dr. M.J. vd Vijver Vrije Universiteit / Academisch Medisch Centrum Dr. E.S. Jordanova Vrije Universiteit
Prof. dr. J.B.M.Z. Trimbos Prof. dr. V.T.H.B.M. Smit Dr. T. Bosse
© M.D. Trietsch, Leiden, the Netherlands
Vulvar squamous cell carcinoma – Genetics, morphology and clinical behaviour
The research described in this thesis was performed at the department of Pathology and the de- partment of Gynaecology at the Leiden University Medical Center, Leiden, the Netherlands.
ISBN: 978-94-6233-769-5
Cover: Esmee Gramberg at AnnaGee Creative Studio (www.annagee.nl) Layout: Rachel van Esschoten, DivingDuck Design (www.divingduckdesing.nl) Printed by: Gildeprint Drukkerijen, Enschede (www.gildeprint.nl)
Content
Chapter 1
General introduction _________________________________________________________ 7
Chapter 2
Designing a high-throughput somatic mutation profiling panel specifically for gynaecological cancers _____________________________________________________ 21
Chapter 3
CDKN2A (p16) and HRAS are frequently mutated in vulvar squamous cell
carcinoma __________________________________________________________________ 43
Chapter 4
Genetic and epigenetic changes in vulvar squamous cell carcinoma and its precursor lesions: A review of the current literature ____________________________ 65
Chapter 5
Spindle cell morphology is related to poor prognosis in vulvar squamous cell carcinoma __________________________________________________________________ 99
Chapter 6
Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas ______115
Chapter 7
Targeted sequencing of primary, metastatic and recurrent spindle cell variant vulvar cancer reveals a highly heterogeneous genetic disease _______________139
Chapter 8
Summary and general discussion ____________________________________________165
Addendum
Nederlandse samenvatting _________________________________________________178 Curriculum Vitae ___________________________________________________________186 List of publications __________________________________________________________187 Dankwoord ________________________________________________________________189
