Pancreatic and Duodenal Homeobox 1 (PDX-1) Expression in Primary Pancreatic Endocrine Neoplasia
R Alvarez, SM Hastings, J-H Chen. Indiana University School of Medicine, Indianapolis, IN
Background: Pancreatic and duodenal homeobox-1 (PDX-1) is a pancreas-specific transcription factor associated with the development and maintenance of endocrine cells. It is expressed in islets as well as in pancreatic neoplasms, and its detection in metastatic endocrine carcinoma is suggestive of spread from a pancreatic origin. However, an evaluation of PDX-1 expression in primary pancreatic endocrine neoplasms has not been performed.
Design: 124 pancreatic endocrine neoplasms from 112 pancreatic specimens are retrieved from the pathology archives of Indiana University. The clinical findings and pathology material are reviewed. The cases are classified according to the current WHO classification of pancreatic endocrine tumors. Immunohistochemical staining for PDX-1 is performed on formalin-fixed paraffin-embedded sections. Nuclear staining intensity for PDX-1 is scored from 0 (negative) to 3+ (strong), with 3+ staining intensity in islet cells serving as an internal reference.
Results: The neoplasms are composed of 25 microadenomas, 70 endocrine tumors, including 35 with uncertain behavior, and 39 endocrine carcinomas (33 well differentiated, 3 poorly differentiated, and 3 mixed exocrine-endocrine carcinomas). 21 tumors are hormonally functioning (15 insulinoma, 5 gastrinoma, and 1 VIPoma) and the remainder non-functioning, including 1 pancreatic polypeptide (PP)-cell neoplasm (PPoma). 25/25 microadenomas exhibit 0 to 1+ PDX-1 staining intensity (average 0.5). PDX-1 expression in pancreatic endocrine tumor and carcinoma was variable and ranged from 0 to 3+. Of these, 3+ PDX-1 staining was observed in 15/15 insulinomas, while its expression is variably diminished in the remaining endocrine tumors and carcinomas (average 0.8 and 1.1, respectively).
Conclusions: Whereas PDX-1 is strongly expressed in pancreatic islets, its expression in pancreatic endocrine neoplasia is variable. PDX-1 staining is strong in insulinomas, supportive of its preserved function in neoplastic beta cells. However, its expression is markedly decreased in endocrine microadenomas, and variably diminished in pancreatic tumor and carcinoma. These results suggest that differential PDX-1 expression and signaling may contribute to the biology and physiology of pancreatic endocrine neoplasia.
Category: Liver & Pancreas
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 208, Monday Morning