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 ant...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19014-w |
| _version_ | 1828143975155892224 |
|---|---|
| author | Blanca Ehms Daniel Kaemmerer Jörg Sänger Stefan Schulz Amelie Lupp |
| author_facet | Blanca Ehms Daniel Kaemmerer Jörg Sänger Stefan Schulz Amelie Lupp |
| author_sort | Blanca Ehms |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T20:08:26Z |
| format | Article |
| id | doaj.art-b944b8685f334282b0fb56eeb7723dbf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T20:08:26Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b944b8685f334282b0fb56eeb7723dbf2022-12-22T04:05:16ZengNature PortfolioScientific Reports2045-23222022-08-0112111010.1038/s41598-022-19014-wReassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61Blanca Ehms0Daniel Kaemmerer1Jörg Sänger2Stefan Schulz3Amelie Lupp4Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University JenaDepartment of General and Visceral Surgery, Zentralklinik Bad BerkaLaboratory of Pathology and Cytology Bad BerkaInstitute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University JenaInstitute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University JenaAbstract 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.https://doi.org/10.1038/s41598-022-19014-w |
| spellingShingle | Blanca Ehms Daniel Kaemmerer Jörg Sänger Stefan Schulz Amelie Lupp Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61 Scientific Reports |
| title | Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61 |
| title_full | Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61 |
| title_fullStr | Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61 |
| title_full_unstemmed | Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61 |
| title_short | Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61 |
| title_sort | reassessment of somatostatin receptor sst4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti human sst4 antibody 7h49l61 |
| url | https://doi.org/10.1038/s41598-022-19014-w |
| work_keys_str_mv | AT blancaehms reassessmentofsomatostatinreceptorsst4expressioninbronchopulmonaryandgastroenteropancreaticneuroendocrineneoplasmsusingthenovelrabbitmonoclonalantihumansst4antibody7h49l61 AT danielkaemmerer reassessmentofsomatostatinreceptorsst4expressioninbronchopulmonaryandgastroenteropancreaticneuroendocrineneoplasmsusingthenovelrabbitmonoclonalantihumansst4antibody7h49l61 AT jorgsanger reassessmentofsomatostatinreceptorsst4expressioninbronchopulmonaryandgastroenteropancreaticneuroendocrineneoplasmsusingthenovelrabbitmonoclonalantihumansst4antibody7h49l61 AT stefanschulz reassessmentofsomatostatinreceptorsst4expressioninbronchopulmonaryandgastroenteropancreaticneuroendocrineneoplasmsusingthenovelrabbitmonoclonalantihumansst4antibody7h49l61 AT amelielupp reassessmentofsomatostatinreceptorsst4expressioninbronchopulmonaryandgastroenteropancreaticneuroendocrineneoplasmsusingthenovelrabbitmonoclonalantihumansst4antibody7h49l61 |