Alternations Of Tumor-related Genes MUC1, PCNA And P53 And Esophageal Cancer Prognosis On The Patients From The High-incidence Area For Esophageal Cancer In Linzhou, Henan

Esophageal carcinoma (EC) is one of the most common malignant diseases in northern China, and Linzhou city (formerly Linxian) is the highest incidence area. The five-year survival rate for early esophageal cancer patients is more than 90%. However, for the patients at late or advanced stage, the five year survival rate is only about 10-15%. So far, traditional prognostic markers, such as cancer stage based on metastasis and pathological grade are still used to evaluate the prognosis of esophageal cancer patients. But, it has been well recognized that there is discordance between the traditional prognosis biomarkers and the actual prognosis, for example, the patients with well differentiation may have a worse prognosis than those with poorly differentiation, indicating the limitation for those markers in prognosis. With the development of molecular biotechnology, many new measurements have been applied in cancer prognosisresearch. It would be much helpful for patients and their family, doctors in charge of the patients and science research to detect molecular changes of esophageal carcinoma related genes, to screen prognosis factors with high sensitivity and specificity and to present individual prognosis information. Studies on esophageal carcinoma prognosis have been expanded in recent years; however, information of molecular mechanisms involved in esophageal cancer prognosis, especially the survival analysis on the subjects from high-incidence area for esophageal cancer was very limited. To further characterize the possible relationship between the molecular changes and esophageal carcinoma prognosis and to elucidate the possible mechanisms of esophageal carcinoma carcinogenesis, the present study was undertaken to follow up esophageal carcinoma patients from high-incidence area, and to determine the alternation of MUC1, PCNA and p53 and prognosis with histopathological and immunohistochemical methods. Combining clinical information with different molecular changes, esophageal carcinoma patients' survival risk was analyzed, to provide the theoretical basis and strategies for clinical biotherapy and preventions. Materials and Methods:One hundred and fourteen patients with esophagealcarcinoma, who had undergone esophagectomy at the Esophageal Carcinoma Hospital of Linzhou City between 1993 and 1996 were enrolled in this study. All the patients had not received radiation therapy or chemotherapy before surgery. There were 66 men and 48 women. The mean age was 53.5+8.1 years for males and 53.6+7.8 years for females, and the age range was 37-72 and 40-69, respectively. All the patients were local residents of Linzhou city, and were followed up for survival after surgery until March 2001, at which the patients had survived more than 5 years or died within 5 years after surgical treatment. 57 patients who survived less than 5 years were all died of recurrence or metastasis, without other serious diseases, accident and obvious causation. All tumor samples were fixed with formalin and embedded with paraffin. Each block was sectioned serially at 5 um, one of which was stained with hematoxylin and eosin for histopathological analysis by two pathologists and the others were used for immunostaining (ABC). Chi-squared test was performed to evaluate association between local lymph node metastasis and expression of MUC1 protein, Kaplan-Meier and life table were used for survival analysis, and multivariate analysis for screening prognosis factors. The significant difference was considered when the p value was less than 0.05.Results:Among 114 esophageal carcinoma patients followed up,there were 37 cases survived 5 year (33%), 57 cases died within 5 years after surgical treatment (50%) and 20 cases were censored during the follow-up (17%).The positive immunostaining rate for MUC1 was 79%(90/114), and the high-expression rate was 63% (72/114). The mean survival time (months) and 95% confident interval of esophageal carcinoma patients with MUC1 high- and low-expression were 41 (35, 47) and 52 (45, 59)...