TY - JOUR
T1 - The search for the primary tumor in metastasized gastroenteropancreatic neuroendocrine neoplasm
AU - Kaemmerer, D.
AU - Posorski, N.
AU - von Eggeling, F.
AU - Ernst, G.
AU - Hörsch, D.
AU - Baum, R. P.
AU - Prasad, V.
AU - Langer, R.
AU - Esposito, I.
AU - Klöppel, G.
AU - Sehner, S.
AU - Knösel, T.
AU - Hommann, M.
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media Dordrecht.
PY - 2014/10/15
Y1 - 2014/10/15
N2 - Gastroenteropancreatic neuroendocrine tumors (NETs) often present as liver metastasis from a carcinoma of unknown primary. We recently showed that primary NETs from the pancreas, small intestine and stomach as well as their respective liver metastases differ from each other by the expression profile of the three genes CD302, PPWD1 and ABHB14B. The gene and protein expression of CD302, PPWD1, and ABHB14B was studied in abdominal NET metastases to identify the site of the respective primary tumors. Cryopreserved tissue from NET metastases collected in different institutions (group A: 29, group B: 50, group C: 132 specimens) were examined by comparative genomic hybridization (Agilent 105 K), gene expression analysis (Agilent 44 K) (groups A and B) and immunohistochemistry (group C). The data were blindly evaluated, i.e. without knowing the site of the primary. Gene expression analysis correctly revealed the primary in the ileum in 94 % of the cases of group A and in 58 % of group B. A pancreatic primary was predicted in 83 % (group A) and 20 % (group B), respectively. The combined sensitivity of group A and B was 75 % for ileal NETs and 38 % for pancreatic NETs. Immunohistochemical analysis of group C revealed an overall sensitivity of 80 %. Gene and protein expression analysis of CD302 and PPWD1 in NET metastases correctly identifies the primary in the pancreas or the ileum in 80 % of the cases, provided that the tissue is well preserved. Immunohistochemical profiling revealed CD302 as the best marker for ileal and PPWD1 for pancreatic detection.
AB - Gastroenteropancreatic neuroendocrine tumors (NETs) often present as liver metastasis from a carcinoma of unknown primary. We recently showed that primary NETs from the pancreas, small intestine and stomach as well as their respective liver metastases differ from each other by the expression profile of the three genes CD302, PPWD1 and ABHB14B. The gene and protein expression of CD302, PPWD1, and ABHB14B was studied in abdominal NET metastases to identify the site of the respective primary tumors. Cryopreserved tissue from NET metastases collected in different institutions (group A: 29, group B: 50, group C: 132 specimens) were examined by comparative genomic hybridization (Agilent 105 K), gene expression analysis (Agilent 44 K) (groups A and B) and immunohistochemistry (group C). The data were blindly evaluated, i.e. without knowing the site of the primary. Gene expression analysis correctly revealed the primary in the ileum in 94 % of the cases of group A and in 58 % of group B. A pancreatic primary was predicted in 83 % (group A) and 20 % (group B), respectively. The combined sensitivity of group A and B was 75 % for ileal NETs and 38 % for pancreatic NETs. Immunohistochemical analysis of group C revealed an overall sensitivity of 80 %. Gene and protein expression analysis of CD302 and PPWD1 in NET metastases correctly identifies the primary in the pancreas or the ileum in 80 % of the cases, provided that the tissue is well preserved. Immunohistochemical profiling revealed CD302 as the best marker for ileal and PPWD1 for pancreatic detection.
KW - Carcinoma of unknown primary
KW - Genetic profile
KW - Microarray
KW - Neuroendocrine tumors
UR - http://www.scopus.com/inward/record.url?scp=84911006486&partnerID=8YFLogxK
U2 - 10.1007/s10585-014-9672-3
DO - 10.1007/s10585-014-9672-3
M3 - Article
C2 - 25098566
AN - SCOPUS:84911006486
SN - 0262-0898
VL - 31
SP - 817
EP - 827
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 7
ER -