1. ¹Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy
2. ²Department of Molecular and Clinical Endocrinology and Oncology, 'Federico II' University, Naples, Italy
3. ³Section of Anatomic Pathology, Department of Human Morphology, University of Insubria and Ospedale di Circolo, Varese, Italy
4. ⁴Department of General Pathology, Medicine, Human Pathology and Clinical Pathology, University of Naples 'Federico II', Naples, Italy
5. ⁵Department of Nuclear Medicine, Ospedale di Circolo, Varese, Italy

Correspondence: Dr M Volante, MD, Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin Medical School, Regione Gonzole 10, Orbassano 10043, Torino, Italy. E-mail: marco.volante@unito.it

Received 17 March 2007; Revised 7 August 2007; Accepted 9 August 2007; Published online 14 September 2007.

Abstract

Typing somatostatin receptor expression in neuroendocrine tumors is of relevance to target somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect somatostatin receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare somatostatin receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different somatostatin receptor antibodies, 107 cases of neuroendocrine tumors with available somatostatin receptor scintigraphy data and pathological material were retrospectively analyzed for somatostatin receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to somatostatin analogue treatment. Restricting 'positive cases' to the presence of a membrane pattern of staining, an overall somatostatin receptor type 2A immunohistochemistry/somatostatin receptor scintigraphy agreement of 77% (² test P<0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of somatostatin receptor expression heterogeneity. Pure somatostatin receptor type 2A cytoplasmic staining showed poor correlation with somatostatin receptor scintigraphy (54% concordance rate). The immunohistochemical detection of somatostatin receptor types 3 and 5, which showed almost exclusively a cytoplasmic pattern, did not improve the concordance with scintigraphic data. In a pilot series, somatostatin receptor type 2A immunohistochemistry correlated with clinical response in 75% of cases. In conclusion, we propose a scoring system for somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors correlated with in vivo data, based on the evidence that only membrane (rather that cytoplasmic) staining should be considered for a reliable, standardized and clinically relevant report.