Changes Of P53,PCNA And Histochemistry In Intestinal Metaplasia And Gastric Cardia Adenocarcinoma (GCA) From Patients At High-incidence Area For GCA In Henan

Gastric cardia adenocarcinoma (GCA) is one of the most common malignant digestive diseases in northern China. A remarkable epidemiological characteristic for GCA is its very similar geographic distribution with esophageal squamous cell carcinoma (ESCC). In contrast to the strikingly decline of incidence of distal gastric cancer around the world in the past two decades, the incidence of GCA, especially in America and Europe, increased dramatically. The incidence of esophageal-gastric-junction cancer has increased to 6-folds with a speed of 20% annually, one of the fastest increasing malignant diseases. The reason is not clear yet. There are several differentes between GCA and distal gastric cancer in respect of epidemiology, risk factors, histogenesis and clinical characteristics. Therefore GCA should be categorized as a clinically distinct disease. Lack of sensitive biomarkers and techniques for early diagnose, as well as the deficiency of effective and specific treatment and chemo prevention, leads to stable high mortality rate and poor prognosis. It has been well known that intestinal metaplasia (IM) is related with distal gastric cancer and has been considered as precancerous lesion for this cancer. Mass survey and follow-up studies by us have showed that IM in gastric cardia tissue, especially in resected cancer tissues was very common in subjects at HIA in Henan. But, the relationships between IM and GCA have not been well characterized and theinformation for molecular basis of GCA is very limited. So far, GCA classification based on different IM types has not been reported. The present study is undertaken to determine the expression of P53 PCNA proteins and mucus proteins in biopsy tissues and surgically resected GCA tissues from the subjects in Linzhou, Henan, the high incidence area (HIA) for GCA, to characterize the relationship between GCA and IM, and to further understand the main molecular alterations in the pathogenesis of GCA.Materials and methods:Three hundreds and twenty gastric cardia biopsy tissues were enrolled from endoscopic mass survey on symptom-free subjects (age > 30 years old) in Linzhou, Henan, HIA for GCA in 2002; 70 surgically resected GCA tissues were enrolled from GCA patients in Linzhou City Hospital, Linzhou Central Hospital and Yaocun Esophageal Cancer Hospital in Henan in 2001. Either chemotherapy or radiotherapy had not been treated on all the patients before operation. All the biopsy tissues and resected tissues were fixed with 85% alcohol, paraffin embedded and serially sectioned for histopathological diagnosis. Histochemical (AB-PAS and HDD-AB methods) and immunohistochemical analysis (ABC method) were applied to the biopsy tissues with IM, the resected tissues with IM adjacent to GCA and resected tissues with GCA, to determine the expression of P53 and PCNA proteins, the type of mucus protein in IM and GCA tissues and the relationship with lesion progress. The X² test and Kappa Test were used for the statistical analysis (P < 0.05 was considered significant).Results:1. The comparison of histochemistry and immunohistochemistry for IM in resected tissues adjacent to GCA and gastric cardia biopsy tissues from symptom-free subjects:(1) The detection rate of IM in resected tissues adjacent to GCA (38.57%) was significantly higher than that in cardia biopsy tissues from symptom-freesubjects (4.38%) at HIA in Henan (P<0.01).(2) The detection rate of incomplete type IM in resected tissues adjacent to GCA (92.59%) was significantly higher than that in cardia biopsy tissues from symptom-free subjects (7.14%) (P<0.01).(3) The detection rate of mild IM in resected tissues adjacent to GCA (62.96%) was significantly higher than that in cardia biopsy tissues from symptom-free subjects (14.29%) (P<0.01).(4) The detection rate of colonic type IM in resected tissues adjacent to GCA (59.26%) was significantly higher than that in cardia biopsy tissues from symptom-free subjects(5) The high positive expression rate of P53 protein (...