Basic principles of molecular biology of cancer cell-Molecular cancer indicators.

Molecular biology of cancer cell is a domain of medical science that is rapidly growing in our days. Knowing the ways and paths that cancer cells follow is crucial to the prevention of cancer itself. Central role to these paths, concerning the cell cycle and the process of apoptosis, has the protein p53. The whole mechanism of the cell cycle is activated by the action of various mitogens, such as growth factors, hormones and cytokines. Carcinogenesis involves alterations of genes (proto-oncogenes and tumor suppressor genes), which encode proteins of the signal transduction. Many of the damages that lead to carcinogenesis may be due to the lack of repressive signals for cell division, but also to the absence of the sensitivity of cells to repressive signals. The cell has mechanisms of receiving apoptotic-antitumor signals and mechanisms of execution of these instructions. A percentage of cancers (4-8%) are etiologically linked to germ (stem) cells mutations and occur at an increased frequency in families (hereditary cancers). Substantial progress in understanding the mechanisms of carcinogenesis, filtration and metastasis of cancer has highlighted the key role of specific genes, primarily oncogenes and tumor suppressor genes.

Expression of Delta Like Ligand 4 (DLL4) in endometrial carcinomas and tumor vasculature.

PURPOSE: Delta like ligand 4 (DLL4) is a transmembrane ligand of the Notch Signalling pathway, that regulates blood vessel sprouting and maturation. We investigated the expression of DLL4 in endometrial cancer. METHODS: DLL4 was assessed in the plasma (with ELISA) and tissues (with immunohistochemistry) 33 patients with endometrial cancer, treated with radical hysterectomy for stage I endometroid carcinoma. The angiogenic activity (AA) of endometrial cancer was quantified by assessing the CD31+ microvessel density (MVD) in the invading tumor front. Vascular maturation index (VMI), defined as the percentage of CD31+ microvessels expressing DLL4, was calculated as the ratio of the CD31+ MVD to the DLL4+ MVD. RESULTS: The angiogenic activity was directly related with the histological grade (p=0.01). The VMI ranged from 0.1 to 0.7 (median 0.34). The concentration of DLL4 in the plasma ranged from 55-81pg/ml (mean 62.8) before, and dropped to 55-62 (mean 58.2) after hysterectomy (p<0.05). DLL4 was also expressed by cancer cells in 17/33 cases. No correlation between DLL4-related parameters with histopathological variables was noted. CONCLUSION: This pilot study shows that DLL4 is overexpressed in endometrial cancer cells, vasculature and is also elevated in the plasma of a fraction of patients before surgery. The percentage of DLL4+ vessels in the penetrating sample ranged from 10-70%, indicating a large difference in the quality of angiogenesis produced between the endometrial tumors of the same histological type and differentiation.