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Somatostatin receptor subtypes in neuroendocrine tumor cell lines and tumor tissues
S Jonas1, M John, J Boese-Landgraf
1Freie Universität Berlin, Universitätsklinikum Rudolf Virchow, Department of Surgery, Germany.
Abstract:
Somatostatin receptor scintigraphy (SRS) is positive in approximately 80% of all patients who have been found to have neuroendocrine (NE) gastroenteropancreatic (GEP) tumors. The reasons for negative results are unclear. The aim of the present study was identification of the specific somatostatin receptor (SSTR) subtypes that are responsible for the in vivo binding of the widely used somatostatin (SST) analogues octreotide and lanreotide in human neuroendocrine gastroenteropancreatic tumors. Ten patients were subjected to SRS with radiolabeled octreotide. Following surgical resection, tumor tissues were analyzed for SSTR subtype mRNA expression by the reverse transcription-polymerase chain reaction (RT-PCR). In addition, SSTR subtype transcripts were investigated by Northern blot analysis and RT-PCR in neuroendocrine tumor cell lines. Expression of SSTR at the protein level was studied by chemical cross-linking experiments. Three patients were negative by SRS. However, RT-PCR revealed most prominently SSTR 2 expression in all tumor specimens. In addition, all tumor tissues analyzed by chemical crosslinking exhibited SST-14 binding sites, indicating that at least some NE tumors were false-negative on SRS.
Insights
Somatostatin receptor scintigraphy (SRS) can be negative in neuroendocrine (NE) tumors. This study found that SSTR 2 expression in tumors may explain false-negative SRS results, despite the presence of somatostatin binding sites.
Area of Science:
- Oncology
- Endocrinology
- Nuclear Medicine
Background:
- Somatostatin receptor scintigraphy (SRS) detects neuroendocrine (NE) gastroenteropancreatic (GEP) tumors in about 80% of cases.
- The reasons for negative SRS results in NE GEP tumors remain unclear.
- Understanding somatostatin receptor (SSTR) subtype expression is crucial for accurate diagnosis.
Purpose of the Study:
- To identify specific SSTR subtypes responsible for octreotide and lanreotide binding in human NE GEP tumors.
- To investigate the correlation between SSTR expression and SRS results.
- To clarify the causes of false-negative SRS findings.
Main Methods:
- Somatostatin receptor scintigraphy (SRS) using radiolabeled octreotide was performed on 10 patients.
- Tumor tissues were analyzed for SSTR subtype mRNA expression via reverse transcription-polymerase chain reaction (RT-PCR).
- SSTR protein expression was assessed using chemical cross-linking experiments.
Main Results:
- Three patients exhibited negative SRS results.
- RT-PCR analysis revealed prominent SSTR 2 expression in all analyzed tumor specimens.
- Chemical cross-linking confirmed somatostatin-14 binding sites in all tumor tissues, indicating potential false negatives on SRS.
Conclusions:
- SSTR 2 is the predominant SSTR subtype expressed in NE GEP tumors.
- The presence of SSTR 2 does not always guarantee a positive SRS result.
- Some NE GEP tumors may be false-negative on SRS due to factors not fully elucidated by current scintigraphy methods.