Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours

Abstract

The increasingly popular use of somatostatin analogs in clinical practice for both diagnostic and therapeutic purposes prompted extensive investigations on somatostatin receptor (sst) expression in human tumors by autoradiography, nucleic acid analysis and, recently, immunohistochemistry (IHC). The currently employed radiotracer for scintigraphy (Octreoscan) is octreotide, a somatostatin analog having a high affinity for sst types 2, 3, and 5. In this study on 25 patients, we compared sst 2, 3, and 5 expression in surgical and biopsy specimens of lung tumors, as revealed by immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR), with the octreoscan outcome (which was positive in 20/25 cases). By IHC, the tumors mainly expressed sst2 (17/25, 68%) at the cell membrane level, while sst 3 and 5 were detected in a fraction of cases (24% and 20%, respectively). Comparing RT-PCR and IHC data, a correlation was found in 83.3% of cases, while octreoscan findings and sst expression were correlated in 22/25 cases (88%). In addition, cytological and biopsy specimens expressed the same sst type found in the corresponding surgical sample, thus indicating that a cell membrane sst immunoreactivity in a biopsy reliably predicts the tumor-receptor profile before its resection. Finally, sst expression was not restricted to neuroendocrine lung tumors, but was also a feature of some non-neuroendocrine carcinomas, although to a lesser extent. The occasional expression of sst subtypes in intratumoral lymphocytes, endothelia and necrotic areas is an additional feature to be considered in the interpretation of Octreoscan findings, since the in vivo procedure does not allow to define the sst cellular distribution. IHC can therefore be usefully coupled to radionuclear investigations to better characterize the sst cellular location and subtype in lung tumors.

Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy

“…In a recent paper, Korner et al 15 tested different somatostatin receptor type 2A antibodies in different human tumors, and correlated the immunohistochemical pattern with previous autoradiographic data on 37 cases, demonstrating a good correlation between the two methods applying the same antibody selected in our study. Previous reports testing somatostatin receptor immunohistochemistry in lung 18 and gastrointestinal 16 neuroendocrine tumors and in pheochromocytomas 17 in correlation to somatostatin receptor scintigraphy are limited by the relative low number of cases compared and by a general lack of standardization of the immunohistochemical interpretation (ie membranous vs cytoplasmic pattern). Therefore, we designed the present study on a large multicentric series of neuroendocrine tumors to validate the reproducibility of the immunohistochemical method and to compare the results with somatostatin receptor scintigraphy imaging.…”

“…In this respect it is difficult, if not useless, to determine which method is more sensitive or specific. It is well known, in fact, that false somatostatin receptor scintigraphy positivity may be related to necrotic areas or inflammation which may be frequent within an otherwise somatostatin receptor negative tumor, 18 and therefore immunohistochemistry represents, rather than an alternative, a useful adjunct to somatostatin receptor scintigraphy. Moreover, the possible role of other somatostatin receptor subtypes (namely types 3 and 5), which possess high affinity for the currently available somatostatin analogues, was investigated, although their analysis did not improve the overall concordance between scintigraphy and immunohistochemistry, and their application in the clinical practice still needs the availability of satisfactory commercial reagents, in our opinion.…”

“…Several studies have documented that generally these methods correlate each other in somatostatin receptors positive cases, with only minor discrepancies. [13][14][15][16][17][18][19][20][21][22] The currently available somatostatin analogues bind preferentially somatostatin receptors type 2 (which is the most widely expressed subtype in neuroendocrine tumors) and to a lower extent types 3 and 5, and somatostatin receptors profiling in individual patients may be of relevance to better tailor the somatostatin analogue-based treatment. This would hopefully allow to increase the response rate of each patient and reduce costs of biotherapy, which are generally high.…”

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

“…Limited evidence for the role of CST in tumour growth control has already been reported [16,17]. Since all immunohistochemically CST-positive tumours did not contain MrgX2 protein, whereas the expression of SRIF receptors (particularly SRIF receptors 2, 3, and 5) and/or GHSR-1a had previously been detected [20][21][22][23][24] in all samples (at either protein or mRNA level), the actions of CST were probably mediated by pathways other than CST/MrgX2 in the tumours investigated.…”

“…The SRIF receptors and GHS-R1a status of most cases of the current neuroendocrine tumour series have been reported previously [20][21][22][23][24]. Additional RT-PCR experiments for SRIF receptors and GHS-R1a were also performed in selected cases, with special reference to non-tumour and neoplastic parathyroid tissue, according to previously published protocols [20,21].…”