Evaluation of the· Role of Tissue inhibitor of Matrix Metalloproteinase (TIMP-1) in Vascular Endothelial Growth Factor (VEGF) induction and their role· in prognosisof breast cancer patients

Abstract

The most common cause of primary tumors is the genetic mutation of one or more cells, resulting in uncontrolled proliferation. The mutated cells have a proliferative advantage over neighboring healthy cells and are able to form a growing mass. The reason for this advantage is not necessarily an increase in the proliferation rate, but may, in some· cases, be a decrease in the cell death rate. < 1> For examp· one of the key functions of tumor suppressor genes such as p53 is to induce apoptosis (programmed cell death) in damaged cells. Loss ofp53, the most commonly·mutated gene in human tumor cells (2), thus allows propagation of damaged DNA <1>.

If the mutated cells remain contained withiri a single cluster, with a well defined boundary separating them from neighboring normal· cells, the tumor is said to be benign, and surgical removal will often provide a complete cure. However, if the tumor cells are inter-mixed with normal cells and attempt to invade the surrounding tissue, the tumor is described. as malignant (3>. Figure 1 shows schematically the difference between a benign and a malignant tumor; only a malignant tumor constitutes a cancer. In this case, surgery is not guaranteed to be successful because the tumor does not possess a well defined boundary and the presence of a single mutated cell could be enough to regenerate the tumor colony <1>. Departure of mutated cells from the primary site represents the transition from in situ to invasive growth and is a key event in cancer progression. Subsequent entry of tumor cells into the blood stream or lymphatic system allows access to remote parts of the body and may lead to the formation of secondary tumors(metastases), making treatment very difficult. <4>

Cancers are categorized by the cell type from which they arise. Those arising from epithelial cells (cells covering the external surface of the body and lining internal cavities) are called carcinomas and are by far the most common form of cancer. Those arising from muscle cells or connective tissue are called sarcomas, whilst cancers arising from haemopoietic cells (precursors of all blood cells) are called leukaemias. (I)