| Background and objectiveThe incidence of primary gallbladder cancer has been increasing in recent years Because of a lack of specific symptoms, many patients have been misdiagnosed and therefore have lost the opportunity to receive timely therapy. The prognosis for most of the patients was quite poor. Even with today's advanced diagnostic methods, early stage gallbladder cancer is still difficult to detect. Thus, Preventive cholecystectomy for patients of gallstones was advised by most of surgeons to improve the poor prognosis of this disease. However, there is some morbidity, such as biliary injury, associated with the operation, so those who need to receive the preventive cholecystectomy need to be defined.Contracted cholecystitis refers to a macroscopically contracted gallbladder with thickening of its wall and often full of gallstones. Its normal tissue is replaced by connective tissue in almost all wall layers. It is thought that Contracted cholecystitis might be a precursor lesion of gallbladder cancer.Identification of proliferative activity may be useful to predict the malignant potential of some of these gallbladder. Proliferative cell nuclear antigen (PCNA) is a stable cell cycle related nuclear protein, which is increasingly expressed in late G, and throughout the S-phase of the cell cycle. Its rate of synthesis is correlated with the proliferative rate of cells. The mouse monoclonal antibody Ki-67 detects an antigenic epitope of a nuclear matrix protein which appears in all cell cycle phases except G0 and early Gi. It was suggested by some previous studies that PCNA and Ki-67 were increased in several malignant tumors including carcinoma of gallbladder.In order to identify the malignant potential of contract cholecystitis, and support for performing preventive cholecystectomy, we investigated the cell proliferative activity in contracted cholecystitis, and then evaluated the relationships between PCNA and Ki-67 expression and several clinicopathological agents such as patient's gender and age. course of disease, thickness of gallbladder wall and diameter of gallstone.Material and methodsParaffin embedded tissues from 72 patients who had undergone cholecystectomy at our department for contracted cholec3'stitis between Jan 2001 and Jan 2002 were studied. We also observed 10 cases of chronic cholecystitis (non-contracted cholesyctitis) and 10 cases of primary gallbladder carcinoma (Nevin II-IH). Expression of PCNA and Ki-67 were detected by immunohistochemical En-Vision method with 1:1000 dilution of PCNA and 1:50 of Ki-67. Positive and negative controls were designed.For each antibody, nuclei staining brown were regarded as positive. At least 1000 epithelial cell were evaluated for PCNA and Ki-67 staining.Statistical analysis was performed using the independent t test and chi-square test.Results1. PCNA labeling index (PCNA LI) in contracted cholecystitis is 47.03?8.15%, was significantly higher than that in chronic cholecystitis (32.90?.11%), p<0.05. PCNA LI in primary gallbladder carcinoma is 90.10?.13%, significantly higher than contracted cholecystitis, p<0.01. Ki-67 positivity in contracted cholecystitis (56.9%, 41/72) is higher as compared to only 10%(1/10) in chronic cholecystitis, but lower than primary gallbladder carcinoma (100%).2. The contracted cholecystitis patients who were older than 50 years old had a significantly higher PCNA LI (54.08?4.99)% and Ki-67 positivity (76.3%, 29/38) than those who under 50 years (PCNA LI: (39.15?8.33)%; Ki-67 positivity: 35.3%, 12/34). Patients with a history of chronic cholecystitis over 5 years had a significantly higher PCNA LI (55.56?5.07)% and Ki-67 positivity (81.4%, 35/43) than those under 5 years (PCNA LI: (34.38?4.74)%; Ki-67 positivity: 20.7%, 6/29). Patients with gallbladder wall thicker than 0.4cm had a significantly higher PCNA LI (53.85?3.19)% and Ki-67 positivity (72.7%, 40/55) than those thinner than 0.4 cm (PCNA LI: (24.94?4.00)%; Ki-67 positivity: 5.9%, 1/17). Patients h...
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