Relationship Between Sex Hormones, Sex Hormone Receptors And Esophageal Carcinogenesis

Esophageal carcinoma (EC) is one of the six most common malignant diseases in the world, with a remarkable geographical distribution and differerce between male and female patients (male: female ratio =2-20:1). Although most of the EC patients are older than 50, young EC patients( =Ss 40 years old)are not uncommon, and incidence for young EC patients seems increasing. These phenomena have issued many important academcic questions: what is the mechanism determining the sex differerce between male and female patients in EC? Is there a unique susceptible gene in young patient which is not, or less involved in older patient? But related information, however, is very limited. It has been well known that esophageal carcinogenesis is a multistage and progressive process. The early indicator for the subjects predisposed to EC is esophageal epithelial cell hyper-proliferation, morphologically manifested as basal cell hyperplasia (BCH), dysplasia (DYS), and carcinoma in site (CIS), the molecular mechanism involved in this process was still unclear. Sex hormones and their receptors are important factors to determine sex difference. An very interesting phenomenon is that sex hormone receptor expression in the normal esophageal epithelium while exprssed in EC tissue However, the expression of sex hormones and their receptors during the multistage progression to EC has not been well characterized. To further elucidate the possible mechanisms of esophageal carcinogenesis, the present study was undertaken to analyse the characteristics of sex hormones and their receptors in the process of esophageal carcinogenesis, to determine the role of sex hormones and their receptors during the multistage progression to EC, and to provide the dependable basis and means for endocrinotherapy and secondary prevention.1.2.1 Material and MethodSymptom-free subjects from high incidence area (HIA) and low incidence area (LIA) were enrolled for mass survey, including 60 (30 for male, 30 for female) cases from HIA and 60 (30 for male, 30 for female) cases from LIA. Forty-four cases of the surgically resected EC are from HIA, (29 male, 15 female). Blood samples were collected from all cases at 7AM, serum levels of estradiol (E2) and testosterone (T)were determined by radiommunoassay (RIA). 142 cases of the surgically resected EC samples were collected from the local hospital in HIA. All the specimens were fixed with 85% ethanol, paraffin embedded, and serially sectioned for morphology and immunohistochemistry (ABC) analysis. The difference in immunoreactivity of ER and PR and its correlation with lesion progression was determined on the subjects from HIA, and ER proteins were detected by Western Blot techquies in 9 specimens of the normal esophageal epithelium and the tissues with different degrees of severity. The X2 test, t test, logistic regrssion test and chi-square test were used for the statistic analysis. ( p<0.05 was considered significant).1.2.2 Results1.2.2.1 Serum levels of sex hormoneSerum levels of estradiol in male from symptom-free subjects at LIA and HIA were 70.500±11.300, 54.684±18.159 (pg/ml), respectively; Serum levels of estradiol in female from symptom-free subjects at LIA and HIA were 87.010±13.910 and 52.044±21.790 (pg/ml). Serum levels of estradiol in male and female EC patients at HIA were 42.330±16.016 and 32.998±19.339 (pg/ml). Serum levels of estradiol in both male and female decreased gradually in the three groups and the difference was significant between each group (p<0.01). Serum levels of testosterone in male from symptom-free subjects at LIA and HIA, were 4.100±1.500 and 5.485±2.485, respectively; Serum levels of testosterone in female from symptom-free subjects at LIA and HIA, were 0.618±0.076 and 1.795±0.959 (pg/ml). Serum levels of testosterone in male and female EC patients at HIA were 5.555±2.648 and 1.985±0.990 (pg/ml). Serum levels of testosterone in both male and female decreased gradually in the three groups and the difference was significant between each group (p<0.01). T...