The objective of this study was to evaluate the reproducibility of the biopsy sampling procedure in research on esophageal lesions. Biopsies were ta ken from the middle and lower thirds of the esophagus, one from each site, from 25 subjects in a high-incidence area for esophageal cancer in Xinye County of Henan Province, China. The biopsy sampling procedure was repeated on the same subjects 10 days later. When the biopsies were analyzed together and those with worse pathologies were used for diagnosis, 52% of the subjects had the same grade of lesions in the second biopsy examination, 32% had lower-grade lesions, and 16% had higher-grade lesions.

In order to characterize p53 alterations in esophageal cancer and to study their roles in carcinogenesis, we performed gene mutation and immunohistochemical analysis on 43 surgically resected human esophageal specimens, which contain squamous cell carcinoma (SCC) and adjacent non-cancerous lesions, from a high-incidence area of Linzhou in Henan, China. A newly developed immunohisto-selective sequencing (IHSS) method was used to enrich the p53 immunostain-positive cells for mutation analysis. p53 gene mutations were detected in 30 out of 43 (70%) SCC cases. Among 29 SCC cases that were stained positive for p53 protein, 25 (86%) were found to contain p53 mutations. In five cases of SCC with homogeneous p53 staining, the same mutation was observed in samples taken from four different positions of each tumor. In a well differentiated cancer nest, p53 mutation was detected in only the peripheral p53-positive cells. In tumor areas with heterogeneous p53 staining, either the area stained positive for p53 had an additional mutation to the negatively stained area or both areas lacked any detectable p53 mutation. In the p53-positive non-cancerous lesions adjacent to cancer, p53 mutations were detected in seven out of 16 (47%) samples with basal cell hyperplasia (BCH), eight out of 12 (67%) samples with dysplasia (DYS), and six out of seven (86%) samples with carcinoma in situ (CIS). All mutations found in lesions with DYS and CIS were the same as those in the nearby SCC. In seven cases of BCH containing mutations, only three had the same mutations as the nearby SCC. The results suggest that p53 mutation is an early event in esophageal carcinogenesis occurring in most of the DYS and CIS lesions, and cells with such mutations will progress to carcinoma, whereas the role of p53 mutations in BCH is less clear.

dies with calcium and decaffeinated green tea (DGT). Each group included 200 subjects (100 sub-jects for treatment, and 100 subjects of placebo). In calcium group, each subject received and oral supplementation of 1, 200mg of calcium daily for 11 months. In DGT group, each subject received 5mg of DGT daily for 12 months. In placebo group, each subject received placebo pill for 11 months (calciurn group) and 12 month (DGT group). At the entry and end trial, esophagecal biopsy specimens were taken at the middle and the lower thirds of the esophagus and from macroscopic iesions, if only, of each subject. Resulet: DGT trail did not show apparent difference between the treatment and placebo group in alleviatin the esophageal precancerous lesions and abnormal cell proliferation. For the calcium intervention study, after 11 years'follow-up. 10 subjects had developed into can-cers in the calcium group (10%, 8 EC and 2GCA), and 8 subjects developed into EC in the placebo group (8%). All these patients were diagnosed at very early stage of cancer (symptom-free). Of the 578 subjects, 25 (18 males and 7 females) had developed into EC (n=23, 43%) and gastric cardia cancer (GCA, n=2, 0.3%), during the 11 years'follow-up. The mean time of cancer development (from entry of the follow-up strdy to the detection) was 5.0±2.9 years (males) and 4.7±3.2 years (females). Of the 25 patients with EC and GCA, 11 were from the 387 followed subject with "normal" histomorphology of biopsy at the entry of the follow-up study (3%, 11/387), 2 were from the subjects with basal cell hyperpla-sia, grade 1 (BCH1, 2%, 2/94), 7 from the subjects with BCH grade Ⅱ (BCHⅡ, 10%, 7/72), and 5 from BCH Ⅲ and dysplasia (20%, 5/25). Conclusions: DGT trail was not shown to have beneficial effects in alleviation esophageal precancerous was not shown to have beneficial effects in alleviating esophageal precancerous le-sions and abnormal cell proliferation patterns. Calcium supplementation did not produce apparent long-term effects on EC. BCH Ⅱ could be considered as precan-cerous lesions of EC. The quantitative histopathological analysis in terms of num-ber of proliferating basal cell layers is importance in determining the high-risk subjects for EC and evaluating the intervention results. Follow-up studies with repeated endoscopic biopsies are the powerful strategy for early detection and mortality control of EC and GAC in the high incidence area.