CA19-9 is a glycoprotein epitope on the sialyl Lewis a structure functioning as a ligand for the adhesion molecule E-selectin. CA19-9 is normally present on the apical surface of the ductal epithelium of the breast, salivary, and sweat glands beside the glands of gastrointestinal mucosa.

CA19-9 strongly stains pancreatic, hepatobiliary, and gastrointestinal adenocarcinomas but lacks the specificity for these carcinoma types. CA19-9 has a very wide expression spectrum as it is found in many other carcinomas of different origin. Consequently, the diagnosis of primary pancreatic carcinoma must be supported by a complete immunohistochemical panel.

PDX-1 (pancreatic and duodenal homeobox 1) [2] also known as insulin promoter factor 1 is a transcription factor involved in the pancreatic development and maturation of the endocrine β-cells in addition to Brunner’s glands, duodenal papilla, and bile ducts. In adult tissue, PDX-1 is intensely expressed in endocrine cells of the upper gastrointestinal tract and pancreas in addition to pyloroduodenal and pancreatic duct mucosa (Fig. 8.1). PDX-1 strongly labels pancreatic endocrine tumors and pancreatobiliary adenocarcinomas including adenocarcinoma of the gallbladder and cholangiocarcinoma. Weak expression of PDX-1 is also found in a subset of colorectal adenocarcinomas. Focal weak PDX-1 expression may be also found in the prostatic glands, lung and breast epithelium, thyroid, liver, spleen, kidney, and skin.

S100P protein is one of the members of the S100 protein family consists of 95 amino acids primarily isolated from human placenta [4]. Besides the placenta, S100P is also expressed in many other types of normal tissue including the myocardium and skeletal muscle and epithelial cells of gastrointestinal tract and prostatic gland as well as the kidney, bladder, and leukocytes. S100P is also expressed in various tumor types such as non-small-cell lung carcinoma, breast carcinoma, pancreatic carcinoma including pancreatic ductal adenocarcinoma, pancreatic intraductal papillary mucinous neoplasm and preneoplastic cells, gastric and colorectal adenocarcinoma, transitional cell carcinoma, ovarian carcinoma, and melanoma [5–8]. Normal breast tissue and normal and inflamed pancreatic tissue lack the expression of S100P. This wide expression profile makes S100P a useful marker for the diagnosis of pancreatic and breast adenocarcinomas especially on small biopsies and FNP. S100P is negative in pancreatic endocrine tumors and acinar cell carcinoma. Prostatic carcinoma and renal cell carcinoma are usually negative for S100P. The expression of S100P is usually associated with a poor prognosis.