**Molecular Biology of Endometrial Carcinoma**

#### Ivana Markova and Martin Prochazka

*Department of Medical Genetics and Fetal Medicine, Palacky University Medical School and University Hospital Olomouc Department of Obstetrics and Gynecology, Palacky University Medical School and University Hospital Czech Republic*

## **1. Introduction**

The term tumour is understood as a general denomination for newly formed tissue formation or cell populations in an organism that do not develop as a physiological response to external or internal stimuli, show abnormality signs and more or less escape the regulatory influence of the surrounding cells and organism. Currently, a general opinion has been accepted that tumours result from congenital or acquired genetic damage. Thus, the spectrum of formerly suggested theories of carcinogenesis has narrowed down to a single genetic theory. It is therefore necessary to emphasize that regardless of malignant growth being sporadic for the individual or recurrent for many family members as a hereditary trait, it is clearly a genetic disease.

#### **2. Molecular principles of tumour genesis**

The process of tumour development consists of several stages and is determined by the imbalance between the cell proliferation and cell death. The cells proliferate if they undergo a cell cycle and mitosis, whereas the destruction, due to a programmed cell death, removes cells from tissues through a standard DNA fragmentation process and cell suicide called apoptosis. These processes of cell division and cell death are regulated by a number of genes. According to the extensive research of several recent decades it is the mutation in genes controlling the cell proliferation and death that is responsible for cancer.

In most malignant tumours mutations appear in a single somatic cell in which, during subsequent division, genetic errors are cumulated, i.e. multistep carcinogenesis. More rarely, if the malignity occurs under the hereditary syndrome with tendency towards malignant tumours, the initial mutations causing cancer are inherited in the germinal line and are therefore present in every cell in a body. Different types of genes participate in the initiation of the tumorous process, e.g. genes coding proteins of signal pathways for cell proliferation, cell cycle regulators or proteins responsible for detecting and correcting mutations. As soon as the malignant growth is triggered by any mechanism, it develops as accumulation of other genetic changes through mutations of genes coding the cell apparatus that repairs damaged DNA and maintains cytogenetic stability. The damage to these genes results in further impairment in cascaded mutations of the increased number of genes controlling cell proliferation and repairing damaged DNA. The original clone of neoplastic cells may, in this way, develop into many sublines with a different degree of malignity. Thus, the cell clone able to survive is selected, i.e. clonal selection. Such tumorous cells generally acquire the ability of invasive growth and metastases.

Each malignant tumour is a mixture of cells with various characteristics as, during the excessive and mostly chaotic and imprecise division, other changes are cumulated and new characteristics acquired. Therefore, the metastatic cells do not reveal different genetic changes than the cells of the original tumour. However, all these cells emerged through the division of a single originally maligned cell and thus the tumour is termed as monoclonal.

The above indicates that the complex tumorous process involves a great number of genes. The main events starting from the carcinogenesis initiation stage to propagation and metastases include activation of proto-oncogenes, inactivation of tumour suppressor genes, microsatellite instability, aneuploidy and loss of heterozygosity (Kolář et al., 2003, Nussbaum et al., 2004).
