Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours

Zamora, Víctor; Cabanne, Ana; Salanova, Rubén; Bestani, Claudia; Domenichini, E; Marmissolle, F.; Giacomi, N; O’Connor, Juan Manuel; Méndez, Guillermo; Roca, Enrique

doi:10.1016/j.dld.2009.07.018

Cited by 61 publications

(63 citation statements)

References 27 publications

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“…Studies directly comparing pancreatic and gastrointestinal NET did not reveal significant differences in the expression of all five sstrs between the two groups [14,15], consistent with the findings of our study. Correlating the sstr1–5 immunoreactivity with tumor stages according to WHO classification, a trend to lower receptor immunostaining from WD to PD NET was observed for sstr1, sstr2a and sstr4, which is in agreement with previous results in NET [5,15,64,65] as well as in other tumor types [66,67]. The differences did not reach statistical significance possibly due to the small number of samples analyzed.…”

Section: Discussionsupporting

confidence: 82%

“…In normal pancreatic islets and in neoplastic cells, sstr1, sstr2a and sstr5 immunoreactivity was observed both at the cell membrane and in the cytoplasm, whereas sstr3 and sstr4 were detected almost exclusively in the cytoplasm. This is only partially in agreement with other studies where plasma membrane localization was described for sstr2a only, with sstr1, sstr3, sstr4 and sstr5 showing mainly a cytoplasmic immunostaining pattern [15,38,57]. Possible explanations for the difference in cellular localization include the epitope selected and the antibodies used.…”

Section: Discussionsupporting

confidence: 56%

“…The number of studies comprehensively investigating all five sstrs in a significant number of NET by IHC is limited and usually performed using different reagents and protocols [14,15,38,57,62], thus making results difficult to interpret. Independent of the methodology, the scoring system, and the cut-off for positivity used, there is a general consensus that NET express sstr in the majority of cases and the presence of more than one receptor subtype is common: sstr2 is usually the most frequently expressed receptor followed by sstr1 and sstr5; while the remaining sstr3 and sstr4 are expressed at a lower level or almost absent [14,30,38,58,63].…”

Section: Discussionmentioning

confidence: 99%

“…sstrs are in fact widely distributed in many organs, such as the pancreas and pituitary gland, and in tumors arising from these and other organs [4,5,6,7,8,9,10,11]. The majority of NET express sstrs with a high density and in different combinations [10,12,13,14,15], thus making SSAs a first-line treatment for the relief of symptoms associated with functioning NET [16,17,18,19,20,21,22,23,24]. …”

Section: Introductionmentioning

confidence: 99%

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Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

et al. 2011

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Background: Activation of somatostatin receptors (sstr1–5) by somatostatin and its analogues exerts an inhibitory effect on hormone secretion and provides the basis for the treatment of a range of endocrine diseases such as acromegaly, Cushing’s disease and neuroendocrine tumors (NET). The lack of well-characterized commercially available sstr subtype-specific antibodies prevents routine identification of the sstr expression profile in patients. Methods: We generated and characterized new mouse monoclonal antibodies (mAbs) targeting the five human sstr subtypes using ELISA and immunohistochemistry, and tested their suitability in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples of normal pancreatic tissue and NET. Results: All mAbs were highly specific with no cross-reactivity. The sstr1–5 immunoreactivity in gastrointestinal NET (n = 67) was correlated with clinicopathologic data. With the exception of sstr3, NET were highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a and sstr5 were present at the plasma membrane and in the cytoplasm of tumor cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic. Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor aggressiveness increased. sstr5 showed an opposite pattern, with higher staining in well-differentiated carcinomas compared with well-differentiated tumors. sstr5 immunoreactivity was correlated with the presence of metastases and angioinvasion, suggesting a possible association with more aggressive behavior. Conclusion: Determination of the sstr1–5 by immunohistochemistry using subtype-specific mAbs is feasible in FFPE tissue and may provide a tool for routine clinical practice.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

et al. 2011

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“…Employing a blind evaluation protocol performed by two pathologists, the immunoreactivity of SR2 and SR 5 were evaluated by semi-quantitative scoring system. The extent of staining was accepted as positive (more than 25% of stained cells), focally positive (less than 25% of stained cells, heterogeneously distributed), and negative (absence of staining) (Zamora et al, 2010) …”

Section: Histopathological Methodsmentioning

confidence: 99%

Somatostatin Receptor 2 and 5 Expressions in Gastroenteropancreatic Neuroendocrine Tumors in Turkey

Yerci

Şehitoğlu²,

Uğraş³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Gastroenteropancreatic neuroendocrine tumors (GNs) are slow growing and although their incidence has increased in recent years, they are relatively rarely seen. Somatostatin analogues are used in the treatment of GNs that express somatostatin receptor (SR). We aimed to investigate the expression of SR2 and SR5 in GNs. Materials and Methods: In this study the expression of SR2 and SR5 was investigated immunohistochemically in 49 cases (26 males, 23 females) diagnosed and graded with GN according to the World Health Organization classification 2010. Results: The percentage of SR2 staining was 91.0% in grade 1, 82.8% in grade 2 and 100% in grade 3. On the other hand, the percentage of SR5 staining was 81.8% % in grade 1, 60.0% in grade 2 and 0% in grade 3. According to the tumor localization, the percentages of SR2 expression were as follows: pancreas 85.7%, stomach 100%, small bowel 70%, appendix 85.7% and rectum 100%. The percentages of SR5 expression were: pancreas 61,9%, stomach 37.5%, small bowel 70%, appendix 71.5% and rectum 66.6%. There was a significant negative correlation between ki67 percentage and SR5 expression (r=-0.341, p=0.016). Conclusions: In this study, GNs were found to highly express SR2 and SR5. Although the expression of SR2 and SR5 changed according to tumor localization, the expression of SR2 was higher than the expression of SR5 in GN. There was a significant negative correlation between ki67 and SR5. Accordingly, SR5 may be a prognostic indicator of GN.

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Malignant epithelial tumours of the small intestine

McCarthy,

Sheahan

2024

Morson and Dawson's Gastrointestinal Pathology

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Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours

Cited by 61 publications

References 27 publications

Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

Somatostatin Receptor 2 and 5 Expressions in Gastroenteropancreatic Neuroendocrine Tumors in Turkey

Malignant epithelial tumours of the small intestine

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