Genetic and Molecular Changes in Serous Gynecological Carcinomas – comparison with other histological types, and clinical associations

..................................................................................................................... 7 Introduction ................................................................................................................ 9 Review of the literature ............................................................................................. 10 1. Clinical and histopathological characteristics ........................................................ 10 1.1. Embryological origin ............................................................................. 10 1.2. Ovarian carcinoma ................................................................................. 10 1.3. Endometrial carcinoma .......................................................................... 11 1.4. Fallopian tube carcinoma ....................................................................... 11 2. Cytogenetic and molecular genetic aberrations ...................................................... 12 2.1. Ovarian carcinoma ................................................................................. 12 2.1.1. Cytogenetic findings ................................................................... 12 2.1.2. Molecular genetic changes ........................................................... 12 2.2. Endometrial carcinoma .......................................................................... 14 2.2.1. Cytogenetic findings ................................................................... 14 2.2.2. Molecular genetic changes ........................................................... 14 2.3. Fallopian tube carcinoma ....................................................................... 15 3. Overview of comparative genomic hybridization (CGH) ....................................... 15 3.1. Methodology ......................................................................................... 15 3.2. CGH studies .......................................................................................... 16 3.2.1. Ovarian carcinoma ....................................................................... 16 3.2.2. Endometrial carcinoma ................................................................ 17 3.2.3. Fallopian tube carcinoma ............................................................. 17 4. Overview of allelic analysis .................................................................................... 18 4.1. Loss of heterozygosity (LOH) ................................................................. 18 4.2. LOH in ovarian carcinoma ..................................................................... 18 4.2.1. Genome-wide analyses ................................................................. 18 4.2.2. Chromosome arm 8p ................................................................... 19 4.2.3. Chromosome arm 18q ................................................................. 19 Aims of the study ...................................................................................................... 21 Materials and methods .............................................................................................. 22 1. Clinical material (I–V) .......................................................................................... 22 2. Methods ................................................................................................................ 22 2.1. Comparative genomic hybridization (I, II) ............................................. 22 2.2. Laser microdissection (III, IV) ................................................................ 23 2.3. Loss of heterozygosity analysis (III, IV) .................................................. 24 2.4. Tumor tissue microarrays (III–V) ........................................................... 25 2.5. Immunohistochemistry (III–V) .............................................................. 25 2.6. Northern blot analysis (III) .................................................................... 25 2.7. Statistical analyses (I, III–V) .................................................................. 25