Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61

Abstract

Somatostatin receptors SST1, SST2, and SST5 are overexpressed in neuroendocrine neoplasms (NENs), but little is known about SST4 expression in NENs because of a lack of specific monoclonal antibodies. We recently developed and thoroughly characterised a rabbit monoclonal anti-human SST4 antibody, 7H49L61, and showed that it is well suited for identifying SST4 expression in routine pathology samples. The present study aimed to re-evaluate SST4 expression in a large set of NEN samples using this antibody. For this purpose, we assessed SST4 expression in 722 formalin-fixed, paraffin-embedded NEN samples from 274 patients by immunohistochemistry using the novel antibody 7H49L61. The immunostaining was semiquantitatively evaluated using the 12-point immunoreactivity score (IRS), and the results were correlated with clinicopathological data. SST4 was detected in 39.3% of all NENs, but with a median IRS of 2.0, its expression intensity was negligible overall. In all cases, both cytoplasmic and membraneous staining was observed. SST4 expression was somewhat higher in bronchopulmonary NEN (BP-NEN) than in gastroenteropancreatic NEN (GEP-NEN) but still very low. SST4 expression positively correlated with favourable patient outcomes in BP-NEN but had a positive association with Ki-67 index or tumour grading and a negative interrelationship with overall survival in GEP-NEN. In conclusion, unlike that of other SST subtypes, SST4 expression in both BP-NEN and GEP-NEN is negligible and of no diagnostic or therapeutic relevance.