Study Of Ornithine Decarboxylase MRNA, Endostatin MRNA And Angiogenesis Expression In Esophageal Squamous Cell Carcinoma And Their Correlation

Background and Objective Esophageal cancer is one of the important causes of malignancy-related death. There are about 150 thousand patients annually die of it in China. Among them 90 % are squamous cell carcinomas. Early detection of tumors has been reported to decrease mortality. However, very little is known about tumor markers and the mechanisms of invasion and metastasis of carcinoma.Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the biosynthesis of polyamines, which are essential for cell proliferation. It is overexpressed in various cancers. Several studies have disclosed that both ODC activity and ODC mRNA expression in esophageal carcinoma are remarkably increased among several kinds of tumors. ODC overexpression is associated with promoting tumor growth and angiogenesis. However the mechanisms by which ODC may regulate invasion and metastasis of carcinoma are still poorly understood.Angiogenesis is an essential process for tumor growth. The concept of tumor angigenesis originally stemmed from Folkman's proposition that tumor growth beyond a few millimeters is dependent on the formation of new blood vessels from the neighboring tissue. Growth of solid tumor has been distinguished into two stages, avascular and vascular. During the angiogenesis stage, the tumors grow rapidly. Angiogenesis is a complex process regulated by a balance between the proangiogenic and antiangiogenic factors.Endostatin, a 20-kilodalton C-terminal fragment of type X VIII collagen, is a strong endogenous angiogenesis inhibitor. It was originally separated from theconditioned media of hemangioendothelioma cells. Endostatin produced by the primary tumor is released into the circulation and may prevent the invasion and metastasis of tumors.The recent studies indicate that ODC-overexpressing human cancer cells showed suppressed expression of endostatin, ODC overexpression facilitates tumor angiogenesis by supressing endostatin. But this hypothesis has not been confirmed.In this study, we investigated the expression of ODC mRNA, endostatin mRNA and microvessel density (MVD) in carcinoma and adjacent normal tissues of the esophageal squamous cancer, and attempted to clarify their clinical significance. In addition, we studied whether there was any correlation among them.Materials and Methods Fresh surgical specimens of 41 pairs of primary esophageal squamous cell carcinomas (T) and adjacent normal esophageal mucosa (N) were obtained. All samples had been proved by means of pathological diagnosis. Reverse transcription-PCR method was used to examine the expression of ODC mRNA and endostatin mRNA , their T:N ratio was calculated after a correction for the T:N ration of B-actin mRNA expression. Immunohistochemical method was used to examine the expression of CD34. Calculated the number of microvessel by anti-CD34 monoclonal antibody to achieve MVD in esophageal carcinoma tissue (T) and correspondingly adjacent normal esophageal tissue (N). Comparisons between groups were performed using Student's Mest when appropriate and the correlation between two continous variables was determined using the Pearson rank correlation (r) test. P value<0.05 was considered significant.Results 1. In 38/41 cases (95.1 %) ,the expression of ODC mRNA was greater in T than in N. The T: N ratio of ODC mRNA, range from 0.87 to 11.3, the average value was 4.69+2.44; 2. The T: N ratio of ODC mRNA expression in esophageal specimens has a significant correlation with tumor size, differentiation, lymph node metastasis and adventitia invasion. There are no correlation between the T: N ratio of ODC mRNA expression and the sex of patients; 3. The cases with tumorsdiameter exceed or equal to 3 cm showed a significantly higher T: N corrected ratio of ODC mRNA than those with the diameter less to 3 cm (P=0.046); 4. The cases with tumors poorer differentiation showed a significantly higher T: N corrected ratio of ODC mRNA than those with better differentiation (P=0.012); 5. The cases of tumors with adventitia infiltration and lymph...