PDX-1, CDX-2, TTF-1 and CK7: A Reliable Immunohistochemical Panel for Pancreatic Neuroendocrine Neoplasms
ES Chan, J Alexander, PE Swanson, MM Yeh. University of Washington Medical Center, Seattle, WA
Background: Neuroendocrine neoplasms (NENs) can occur in virtually all sites of the body. Since NENs arising in different organs share similar morphologic features, attempt to distinguish metastatic vs primary NENs based on morphologic grounds alone is difficult. Pancreatic duodenal homeobox 1 (PDX-1) is a Hox type transcription factor essential for both exocrine and endocrine pancreas differentiation and maintenance of beta-cell function. We investigated PDX-1 as an immunohistochemical marker in primary pancreatic NENs.
Design: 79 primary NENs (25 pancreas, 29 lung, 25 gastrointestinal tract) were studied. Clinical and radiologic data were reviewed to ensure the validity of the stated primary sites. Immunohistochemistry for PDX-1, CDX-2, TTF-1, CK7 and CK20 was performed and results were based on consensus review of two authors blinded to the primary sites.
Results: PDX-1 reactivity was predominantly cytoplasmic, with occasional nuclear labeling. PDX-1 was seen in 19 of 25 (76%) pancreatic NENs; in contrast, only 3 of 29 (10%) pulmonary NENs and 1 of 25 (4%) gastrointestinal NENs were positive. PDX-1 was therefore 93% specific and 76% sensitive for pancreatic NENs (Youden s index = 0.69). TTF-1 was expressed only in pulmonary NENs; all other NENs were negative for TTF-1 (Youden s index = 0.52). CK7 was also very specific (90%) and sensitive (66%) for pulmonary NENs (Youden s index = 0.56). CDX-2 was seen in 21 of 25 (84%) cases of gastrointestinal NENs and only in 1 of 25 (4%) cases of pancreatic NENs. Thus, CDX-2 was 98% specific and 84% sensitive for gastrointestinal NENs (Youden s index = 0.82).
Immunohistochemical profiles of NENs arising in different sites
|Pancreas||19/25 (76%)||1/25 (4%)||0/25 (0%)||3/25 (12%)||3/25 (12%)|
|Lung||3/29 (10%)||0/29 (0%)||15/29 (52%)||19/29 (66%)||1/29 (3%)|
|Gastrointestinal tract||1/25 (4%)||21/25 (84%)||0/25 (0%)||2/25 (8%)||4/25 (16%)|
Conclusions: PDX-1 is highly specific with very good overall diagnostic accuracy for pancreatic NENs. An immunohistochemical panel including PDX-1, CDX-2, TTF-1, CK7 and CK20 may be useful in distinguishing NENs of pancreatic origin from other primaries.
Category: Liver & Pancreas
Tuesday, March 10, 2009 2:00 PM
Platform Session: Section E, Tuesday Afternoon