Carcinomas of the ampulla of Vater are rare and assumed to generally arise from preexisting adenomas (adenoma-carcinoma sequence). Histologically, distinct subtypes can be distinguished that were shown to differ significantly in terms of clinical outcome. Since pathologists usually receive bioptic tissue samples of ampullary tumors obtained during endoscopy, accurate classification of carcinoma subtypes can sometimes be difficult on morphological criteria alone. We therefore performed immunohistochemistry using a panel of established marker proteins (CK7, CK20, p21, p27, ESA, bax, and ephrin-B2) on 175 carcinoma, 111 adenoma, and 152 normal mucosa specimens of the ampulla of Vater and identified distinct immunoprofiles for every carcinoma subtype. Fluorescence in situ hybridization analyses of therapeutic target genes (c-myc, EGFR1, CCND1, HER2) found CCND1 to represent the most frequently amplified gene in our series (7.5%
