AnalysisonAlternationsofMUC-1,C-erbB2,P53andPCNA,Histochemistry Of Intestinal Metaplasia And P53 Gene Mutation In Cancer And Nearby Cancer Tissues From Concurrent Cancers Of The Esophagus And Gastric Cardia In Same Patients From High-Incidence Area

Esophageal squamous cell carcinoma (SCC) and gastric-cardia adenocarcinoma (GCA) are the two most frequent malignant diseases in the world. SCC is characterized by its remarkable geographic distribution, the ratio for its incidence could be as high as 500:1. Consistent geographic distribution with SCC in the same high-incidence area (HIA) is the remarkable epidemiological characteristic of GCA, and in the America and Europe the incidence of GCA increased dramatically in recent decades. Linzhou and nearby counties in Henan province, is the highest incidence and mortality area for SCC and GCA in the world, SCC and GCA remain the leading cause of cancer related death in these areas. It isnoteworthy that the concurrent cancers from esophagus and gastric cardia in same patient (CC) is not uncommon in this area, with an incidence of 0.4-2.5%. This special pathogenesis pattern indicates that there may be same or similar risk factors and mechanism involved in the carcinogenesis. The molecular mechanism of SCC/GCA is still not clear, and the information from the concurrent cancers of SCC & GCA in same patient in the HIA is very limited. It is apparent that to further characterize the molecular changes of CC patients may provide not only more information on the molecular mechanism and also the etiological clues for SCC and GCA.Recent studies indicate that carcinogenesis of SCC/GCA is a mulitistep progressive process involved by multiple genetic changes (accumulation or overlap). The accumulation of p53 protein and p53 gene mutation was observed in the very early stage of esophageal carcinogenesis, even in the microscopically normal esophageal epithelium, with the immunostaining positive and mutation rates increasing with the lesions progression. In Addition, our recently study showed that MUC-1, C-erbB-2 and PCNA protein overexpressions were also observed in the carcinogenesis of GCA.To understand the molecular mechanisms of SCC/GCA carcinogenesis and to expand the knowledge for early detection of SCC/GCA and screening high risk population, the present study was undertaken to analyze the alternation of MUC-1, C-erbB2, p53 and PCNA in protein level, p53 gene mutation in cancer tissues and adjacent cancer tissues with different degrees of precancerous lesions, and the histochemical changes of intestinal metaplasia in the tissues adjacent to GCA on the CC patients.Materials and methods:25 cases with concurrent cancers of SCC & GCA enrolled in this study were from Linzhou City Hospital, Yaocun Esophageal Cancer Hospital and Anyang City Tumor Hospital, the high-incidence area for EC, including 16 males and 9 females, with a mean age 59 (59 + 9.88) in male and 60.6 (60.6 + 11.44) in female . All the patients were not treated by either chemotherapy or radiotherapy before operation. All the resected tissues and biopsy tissues were fixed with alcohol, paraffin embedded and serially sectioned for histopathological diagnosis, histochemical staining, immunostaining and DNA extracting. The diagnosis of CC was based on criteria: 1) the tumors must be clearly separated on histological phenotype; 2) the tumors must be malignancy; 3) Metastasis must be excluded. Three histochemical staining methods, Alcion Blue-Schiff staining (AB-PAS) , Alcion Blue staining (AB(PH=2.5)) and High Iron Diamine staining (HID) were applied respectively to characterize EM in the tissues adjacent to GCA; Immunohistochemistry (ABC) method was undertaken to determine the expression of p53, PCNA, C-erb-B2 and MUC-1 proteins and the relationship with lesion progress; microdissection> PCR and DNA sequencing were applied to analyze p53 gene mutation. The %2 test, Fisher's Exact Test, Mantel-Haenszel x2 Test and Kappa Test were used for the statistics (p<0.05 was considered significant).Results:1. Clinicopathological analysis:Pathologists as primary SCC and GCA in same patient verifiedall the 25 cases. Among 25 CC patients, the sex ratio was 1.78:1. 21 patients were over 50 years old (84%). Of 25 patients, there were 2 (8%) early prima...