Objective To evaluate apoptosis and cell proliferation on cytologic spec- imens (smears) from endoscopic retrograde cholangiopan- creatography in patients with ampulary carcinoma and to correlate that relationship with the grade of the tumors. Study Design Forty patients (23 males and 17 females) aged 45–81 who underwent endoscopic retro- grade cholangiopancreatogra- phy were diagnosed by cytology as having ampullary adeno- carcinoma and the diagnoses were confirmed histologically after an operation. All smears were stained using Papanicolaou and Giemsa stain. Apop- tosis was assessed using terminal digoxigenin-labeled dUTP nick-end labeling (TUNEL assay) and cell proliferation using MIB-1 monoclonal antibody by the alkaline phos- phatase method. Results The TUNEL indices were 0.4 ± 0.07, 0.91 ± 033 and 3.1 ± 0.9 in well, moderate and poorly differentiated am- pullary carcinoma, respectively. The differences in both TUNEL and MIB-1 labeling indices were statistically sig- nificant between well, moderately and poorly differentiated ampullary carcinoma, and a positive correlation was found between TUNEL and the MIB-1 indices. Conclusion Apoptosis (cell death) and cell proliferation increase as the grade of the differentiation de- creases in ampullary carcino- ma, suggesting a rapid turn- over of the tumor cells with lower grates of differentiation, and apoptosis may play an im- portant role in the growth of the tumors in patients with ampullary carcinomas. (Acta Cytol 2010;54:39–42) Keywords: ampulla of Vater, apoptosis, endoscopic retrograde cholangiopancreatography, MIB-1, TUNEL. P rimary carcinomas of the extrahepatic biliary sys- tem (extrahepatic bile ducts, gallbladder and am- pulla of Vater) are important health problems world- wide, and their management presents great challenges to the hepatobiliary specialist. Carcinoma of the am- pulla of Vater is a relatively uncommon tumor and ac- The lower the grade of differentiation in ampullary carcinomas, the more rapid the turnover of tumor cells. Apoptosis and Cell Proliferation Correlated with Tumor Grade in Patients with Ampullary Carcinoma Alexandra Kalogeraki, M.D., Ph.D., Maria Tzardi, M.D., Ph.D., Michael Papadakis, M.D., Efstathios Stathopoulos, M.D., Ph.D., Elias Kouroumalis, M.D., Ph.D., and Odysseas Zoras, M.D., Ph.D. From the Departments of Pathology, Gastroenterology and General Surgery, Voutes-Stavrakia Medical School, Heraklion, Crete, Greece. Dr. Kalogeraki is Assistant Professor, Division of Cytopathology. Dr. Tzardi is Assistant Professor, Department of Pathology. Dr. Papadakis is Pathologist. Dr. Stathopoulos is Associate Professor, Department of Pathology. Dr. Kouroumalis is Professor, Department of Gastroenterology. Dr. Zoras is Associate Professor, Department of General Surgery. Address correspondence to: Alexandra Kalogeraki, M.D., Ph.D., Department of Pathology, Medical School, Voutes-Stavrakia, Heraklion, 71110 Crete, Greece (kalogerakimed@yahoo.gr). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article. Received for publication February 18, 2009. Accepted for publication June 9, 2009. Nongynecologic Cytopathology 0001-5547/10/5401-0039/$21.00/0 © The International Academy of Cytology ACTA CYTOLOGICA 39