Somatostatin receptor profiling in hepatic metastases from small intestinal and pancreatic neuroendocrine neoplasms: immunohistochemical approach with potential clinical utility.
BACKGROUND
The expression of somatostatin receptors (SSTRs) on endocrine tumor (ET) cells forms the basis for somatostatin analog treatment of patients with SSTR-positive, hormonally active ETs. In patients with SSTR-negative ETs, the clinical response is generally absent or suboptimal, while nonfunctioning ETs with SSTR positivity show a variable response to such therapy.


METHODS
We retrospectively studied SSTR subtype expression in hepatic metastases from 14 adult patients with primary endocrine carcinomas (ECAs) of the small intestine and pancreas and compared SSTR subtype expression among the primary and metastatic ECAs. Polyclonal antibodies against the 5 SSTR subtypes were used on formalin-fixed, paraffin sections from each primary and metastatic ECA. Both qualitative and semiquantitative evaluation of the stained ECA sections was carried out.


RESULTS
Eleven (61%) of 18 hepatic metastases from small intestinal and pancreatic ECAs were positive for SSTR-1, 15 (83%) for SSTR-2, 13 (72%) for SSTR-3, 10 (56%) for SSTR-4, and 15 (83%) for SSTR-5. Among 11 hepatic ECA metastases from small intestinal ECAs (carcinoids), 7 (63%) expressed SSTR-1, 9 (81%) expressed SSTR-2, 8 (72%) expressed SSTR-3, 6 (54%) expressed SSTR-4, and 10 (91%) expressed SSTR-5. Of 7 hepatic ECA metastases from pancreatic ECAs, 4 expressed SSTR-1, 6 expressed SSTR-2, and 5 expressed SSTR-3 and SSTR-5 each. We also observed the immunohistochemical evidence of heterogeneity of expression of various SSTR subtypes in the primary enteropancreatic ECAs and their hepatic metastases.


CONCLUSIONS
SSTR subtype expression needs to be correlated to somatostatin analog therapy. Immunohistochemical profiling of various SSTR subtypes as a part of routine surgical pathologic analysis of enteropancreatic ETs may become a useful predictor of responsiveness of ETs to various SSTR analogs.
Nasir
Aejaz
A
Gastrointestinal Tumor Program, Neuroendocrine Cancer Research, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612-9497, USA. anassmir@nc.rr.com
Stridsberg
Mats
M
Strosberg
Jonathan
J
Su
Phi-Huynh
PH
Livingston
Sandra
S
Malik
Humaira A
HA
Kelley
Scott T
ST
Centeno
Barbara A
BA
Coppola
Domenico
D
Malafa
Mokenge E
ME
Yeatman
Timothy J
TJ
Kvols
Larry K
LK
D000328:Adult; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000556:secondary*; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017481:Receptors, Somatostatin / Q000145:classification / Q000378:metabolism*; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives*
D017481:Receptors, Somatostatin; D013004:Somatostatin