| Background and purposeColorectal cancer is the fifth leading cause of cancer death and its incidences are increasing year by year in China, especially in the big cities. Although total mesorectal excision and postoperative adjuvant therapy improve the prognosis, the 5-year survival rate of rectal carcinoma remains around 50%. In recent years, sphincter-saving procedure for rectal carcinoma has been paid great attention to, but the risk of local recurrence after surgery remains around 10%,especially after middle-low anterior resection ,the risk of local recurrence were up to 20.3%~34.6%. Invasion and metastasis, which is one of the biological features of malignant cancer, is the major cause of leading to local recurrence or failure of treatment. Further studies of the mechanisms involved in invasion and metastasis of rectal cancer at molecular level will not only contribute to findinghelpful markers to predict the range of resection and prognosis of rectal carcinoma ,but also contribute to improvement of its poor prognosis and the safety of sphincter-saving procedure for rectal carcinoma Regions of hypoxia are found to exist within many solid tumors, and the extent of intratumoral hypoxia is positively associated not only with invasion, metastasis and poor patient prognosis, but also with resistance to chemtherapy, radiotherapy and immunotherapy. In order to adapt to hypoxic microenvironment, cancer cells must enhance their glucose transport and glycolytic rates and form angiogenesis , which is mediated via hypoxia-inducible factor 1 (HIF-1), a key transcription factor that up-regulates a series of genes and performs both of these functions.HIF-1 is composed of a and P subunits. HIF-1β (also known as the aryl hydrocarbon receptor nuclear translocator) is a common subunit of multiple bHLH-PAS proteins, whereas HIF-1 α is the unique, Oa-regulated subunit that determines HIF-1 activity.The process of angiogenesis is tightly controlled by the net balance of angiogenic stimulators and inhibitors. Among proangiogenic factors, VEGF is the most potent and critical inducer of angiogenesis. HIF-1 α is an upstream transcription factor of VEGF gene. It has been suggested that intratumoral microvessel density (MVD) assessed by immunohistochemical staining for the endothelial antigen could be used as an indirect parameter of angiogenesis. Recent studies have demonstrated that overexpression of VEGF, HIF-1 α and higher MVD are positively associated with invasion, metastasis and poor patient prognosis in many tumors. Therefore, VEGF and HIF-1 α may become the important target of anticancer therapy, which has become the focus of clinical and experimental study and several experimental studies have given promising results. But , to our knowledge, until now ,only few data exist on the correlation of HIF-1 α,VEGF protein expression and MVD with invasion, metastasis and patient prognosis in rectalcancer . The aim of this study was to investigate the expression of HIF-lα, VEGF and MVD in rectal carcinoma and study their correlation with clinical pathological features such as cancer invasion and metastasis, as well as the interaction between them . Materials and methodsFormalin-fixed and paraffin embedded sections of tumor tissue were obtained from 61 patients who didn't received any form of chemotherapy, radiotherapy and immunotherapy before operation and underwent curative resection for rectal carcinoma in Huaihe Hospital, Henan University. The protein expression of HIF-la and VEGF was identified by SABC immunohistochemical method. Immunohistochemical staining for the CD34 endothelial antigen, which was identified by SP immunohistochemical method, was performed to highlight the new growth microvessels and the microvessel density of tumor was calculated. All statistical analyses were carried out with SPSS 10.0 software. The continuous variables were analyzed with student's t test or one way analysis of variance (ANOVA) and categorized data...
|
PDF Full Text Request