[576] Value of Islet 1 and PAX-8 in Identifying Metastatic Neuroendocrine Tumors of Pancreatic Origin.

Jamie Koo, Richard Mertens, Hanlin L Wang, Fai Chung, Deepti Dhall. Cedars-Sinai Medical Center, Los Angeles, CA

Background: Neuroendocrine tumors (NETs) can often present as metastases to the liver before the primary tumor is discovered. While the transcription factors TTF-1 and Cdx2 have been shown to aid in the identification of NETs of lung and gastrointestinal (GI) origin, respectively, no such marker has been established for the detection of NETs of pancreatic origin. Recently, two transcription factors, Islet 1 and PAX-8, have been proposed as markers for pancreatic NETs. The purpose of this study was to evaluate the usefulness of Islet 1 and PAX-8 in distinguishing metastatic pancreatic NETs from those originating from other primary sites, as well as to examine the sensitivity and specificity of TTF-1, Cdx2, Islet 1 and PAX-8 for metastatic NETs from a variety of primary sites.
Design: A total of 69 liver metastases of NETs with known primary sites were studied. The primary sites were established based on prior, concurrent or followup surgical pathology (53) or well documented clinical history (16). Immunohistochemistry was performed using antibodies against Islet 1, PAX-8, TTF-1 and Cdx2. Nuclear staining of at least 5% of tumor cells was considered a positive result. Staining intensity was also scored as weak, moderate or strong.
Results: Immunohistochemistry results are summarized below:

Staining of Metastatic NET in Liver

Site of Primary	TTF-1	Cdx2		Islet 1	PAX-8
		Weak	Mod-Strong
Pancreas (n=22)	1 (5%)	1 (5%)	0	16 (73%)	2 (9%)
Lung (n=7)	4 (57%)	0	0	1 (14%)	2 (29%)
Ileum (n=35)	0	8 (23%)	24 (69%)	0	0
Duodenum (n=1)	0	0	0	0	0
Colon (n=2)	0	0	1 (50%)	0	0
Rectum (n=2)	0	0	0	2 (100%)	0

For metastatic pancreatic NETs, Islet 1 has a sensitivity of 73% and specificity of 94%, while PAX-8 has a sensitivity of 9% and specificity of 96%. For metastatic GI NETs, Cdx2 has a sensitivity of 83% and specificity of 96%. For metastatic lung NETs, TTF-1 has a sensitivity of 57% and specificity of 98%. Islet 1 expression was found in 1 metastatic lung NET and 2 metastatic rectal NETs, and PAX-8 expression was seen in 2 metastatic lung NETs. Of the 3 metastatic lung NETs with aberrant Islet 1 or PAX-8 staining, all 3 also showed strong co-expression of TTF-1. Similarly, the 1 metastatic pancreatic NET with aberrant TTF-1 and Cdx2 staining also showed strong co-expression of Islet 1.
Conclusions: Islet 1 is more sensitive than PAX-8 for the detection of metastatic NETs of pancreatic origin. When used in combination with TTF-1 and Cdx2, Islet 1 is of help in determining the origin of a metastatic NET.
Category: Endocrine

Monday, February 28, 2011 9:15 AM

Platform Session: Section H 1, Monday Morning