Department of Hepatobiliary Surgery, Air Force General Hospital of PLA, Beijing, 100142, China.
Exp Mol Pathol. 2011 Oct;91(2):569-77. doi: 10.1016/j.yexmp.2011.06.004. Epub 2011 Jul 12.
The mucosa of gallbladder stimulated with gallstones and accompanied with abnormalities in bile composition, is the origin of biliary disease, which could induce metaplasia, simple hyperplasia, atypical hyperplasia and even carcinoma in situ and invasive carcinoma in gallbladder mucosa.
To determine the disorder of the balance between cell proliferation and cell cycle or apoptosis in gallbladder cancer accompanied with gallstones, removal of the gallbladder due to gallstones specimens of 88 cases were collected randomly, including a variety of 54 cases for hyperplasia, 27 cases for gallbladder cancer and 7 cases for normal gallbladder. The expressions of key cell cycle factors were detected by in situ hybridization, immunohistochemistry and Western blot.
The expressions of CDK4 and Cyclin D1 increased along with progression of gallbladder mucosa hyperplasia; and showed highest expression in cancer group. On the contrary, p16 decreased to the lowest level in gallbladder cancer. The increased apoptotic index analyzed by TUNEL assay rose along with malignant degree to the highest level in undifferentiated carcinoma.
Our results suggest that changes of these signals have effect on breaking the balance of proliferation and death of gallbladder epithelial cells, even on inducing gallbladder cancer.
受胆结石刺激且伴有胆汁成分异常的胆囊黏膜，是胆系疾病的起源，可能引起胆囊黏膜的化生、单纯增生、不典型增生，甚至原位癌和浸润性癌。
为了确定伴有胆结石的胆囊癌中细胞增殖与细胞周期或细胞凋亡平衡的紊乱，随机收集了 88 例因胆结石而切除胆囊的标本，包括多种增生 54 例、胆囊癌 27 例和正常胆囊 7 例。通过原位杂交、免疫组织化学和 Western blot 检测关键细胞周期因子的表达。
CDK4 和 Cyclin D1 的表达随胆囊黏膜增生的进展而增加，在癌组中表达最高。相反，p16 在胆囊癌中降至最低水平。通过 TUNEL 分析的凋亡指数随恶性程度的增加而升高，在未分化癌中达到最高水平。
我们的结果表明，这些信号的变化影响了胆囊上皮细胞增殖和死亡的平衡，甚至导致了胆囊癌的发生。
