الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most common cancer in women in both developed and developing countries. In Egypt, it has been reported that patients commonly present with more advanced disease at diagnosis. The development of breast cancer is believed to be a multi-step process, sequentially progressing from normal to hyperplastic, to in situ, and to invasive stages. In this aspect,angiogenesis has been described as one of the hallmarks of cancer development.
One of the most important angiogenic factors is vascular endothelial growth factor (VEGF), which is thought to have a crucial role in many of the steps of the angiogenic cascade. It is a protein secreted by nearly all cells and occurs as several isoforms. Its release may to activate endothelia and increase the vascular permeability, allowing escape of proteins into the extravascular space to provide the lattice needed for endothelial migration. Angiogenic mediators produced by tumour and host cells diffuse to nearby existing vessels and bind to endothelial receptors, resulting in endothelial activation and anti-apoptotic molecule expression, an effect mediated primarily by VEGF. The proliferation of activated endothelial cells characteristically leads to sprouting of microvessels. Interestingly, normal breast adjacent to malignant breast induced angiogenesis twice as frequently as did tissues from non-neoplastic breast, suggesting that the angiogenic switch occurs before morphological changes are identifiable. The occurrence and progression of breast cancer may be related with the expression of VEGF.
VEGF, VEGF receptors, and microvessel density are considered as markers for angiogenesis. Using microvessel density as a surrogate for angiogenesis, benign lesions associated with high vascular density are correlated with increased risk for developing breast cancer. It has also been suggested that quantification of angiogenesis might help to predict the likelihood that in situ cancers will progress or that a tumour will respond to treatment, and has been shown to correlate directly with the presence of bone marrow micrometastases and survival.
The current study is directed to explore the possible relationship between the expression level of the vascular endothelial growth factors (VEGF) and the lymphangio/ vascular characteristics of breast cancer and also, to assess their suitability as potential prognostic factors.
To approach this aim, 30 women, with average age of 44 years and histologically proved breast cancer were included in the study .They were subjected to clinico- pathological investigation and full history taking.Routin biochemical investigations including liver and kidney function tests were also carried out .CA 15-3, tumor marker, serum VEGF level and the microvascular density( MVD) were assessed in those patients as angiogenic markers .
In the current study, the results of the routine biochemical investigations, e.g, liver and kidney function tests were within normal range in those patients.The serum level of CA 15-3 in breast cancer patients were within the normal range during the follow up period accompanying the chemotherapy .A positive correlation between CA 15-3 level and patient prognosis has been reported .
The mean serum level of VEGF in breast cancer patients before surgery was significantly higher either than that in healthy women or that in the same patients after surgery for many reasons. The observed increase in serum level of VEGF in breast cancer patients could be attributed to the hypoxic condition associated with the tumor development and progression. Previously , it has been reported that the expansion of a solid tumour including breast cancer, ultimately leads to the development of hypoxic regions, which inturn increases VEGF production and further angiogenesis. Also,it has been reported that VEGF is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. Moreover, it acts as a survival factor not only for endothelial cells, but also for some breast tumour cells, protecting them from apoptosis, particularly under hypoxic stress.
Since, the majority of patients were positive for estrogen receptors, the presence or absence of the ER depends on the specific genetic makeup of the individual tumor, and ER positivity implies a greater likelihood of estrogen responsiveness of the tumor. Thus, the genetic status of a tumor may determine whether or not estrogen can stimulate VEGF expression.
Patients with infiltrative ductal carcinoma (IDC) ,which are usually present in a wide field that may be responsible for the high VEGF levels noted. While infiltrative lobular carcinoma (ILC) of the breast failed to reveal significant VEGF mRNA.
After surgery, the mean serum level of VEGF in breast cancer patients was significantly reduced may be due to the removal of tumor tissue since the source of VEGF is the tumor tissue. However, after surgery the mean serum level of VEGF in breast cancer patients was higher than that in healthy women without reaching a significant level.
Meanwhile, serum VEGF level was not correlated with age, tumor size, nodal status, histological grade or tumor stage.
On the other hand, the results of the present study showed a significant positive correlation between MVD and the number of axillary metastatic lymph nodes, size of tumor and tumor grade While no correlation were found between MVD with ER/PR .Also , the current study revealed the absence of correlation between VEGF level and MVD.
Moreover,the clinical significance of high microvessel density in breast cancer remains uncertain, and the variability in technical approaches and difficulty in distinguishing blood and lymphatic microvessels appears to contribute to this uncertainty. Visual and image cytometric microvessel density counting methods are each associated with key advantages and limitations. For example, microscopic visual counting is less expensive and much more widely available among pathologists, but the inherent subjectivity of this method may limit interobserver reproducibility. However, Chalkley count technique seems to be preferable for estimating angiogenesis with regard to the prognostic stratification of breast cancer patients, based on its strong prognostic impact, and acceptable reproducibility.
There is substantial preclinical and clinical evidence that angiogenesis plays a role in the development of tumors and the progression of malignancies. Inhibiting angiogenesis has been shown to suppress tumor growth and metastasis in many preclinical models. These benefits have translated to the clinic with both marketed and investigational antiangiogenesis agents. The most prominent target of these compounds is vascular endothelial growth factor (VEGF) and its receptors. However, several other factors are of interest as well.
Although there are many ‘antiangiogenic’ targets for anticancer therapies, many therapies have directly targeted the VEGF pathway because of its critical role in pathological angiogenesis and its profound influence of this growth factor on endothelial biology.