Imbalances and loss of heterozygosity (LOH) in endometrial carcinoma detected by array based Copy number variations (aCNV)

Introduction:

Endometrial carcinoma (EmCa) is the most common pelvic malignancy in the western hemisphere accounting for 6% of all cancers in women. Although the prognosis of endometrial-like EmCa is good, the mortality rate of other EmCa types is between 21 – 51%. An earlier detection of EmCa will probably reduce mortality. In order to improve the diagnosis and thus the patient outcomes, we follow the strategy to identify cancer cells by simple techniques like fluorescence in situ hybridization (FISH), obtained by brushing out of vaginal cavity. To generate suitable FISH-probes, it is necessary to know the most common imbalances in EmCa. By using aCGH we were searching for the most common imbalances in EmCa.

Material and Methods:

We collected 24 EmCa samples from Universities Greifswald and Kiel and Institute of Hematopathology in Hamburg as formalin-fixed paraffin-embedded tissue (FFPE) or fresh tissue. In order to cover imbalances of genes suspicious in EmCa [2] we used 4 × 180 k + SNP microarrays optimized in design by oxford gene technology (OGT, Begbroke, UK) with increased resolution.

Results:

We found imbalances in 75% of all analysed EmCa cases in chromosome locations 1q21.3, 9p13, and Xp22.33. Furthermore, we detected imbalances in over 58% of all EmCa cases at location 11p15.5 and 15q11.2. The extent of these suspicious locations identified in EmCa allows the use of Bacterial artificial chromosome (BAC) clones to generate FISH-probes.

Discussion:

Using information from aCGH, it could be possible to generate FISH-probes able to detect EmCa-cells in rear vaginal cavity obtained by brushing. In further studies, we lay the foundations for the generation of multiplex FISH probes and use them on these cells. We plan to test identifying cancer cells from the preparation of rear vaginal cavity brushing by using our FISH-probes.