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Determination of Somatostatin Receptor Subtype 2 in Carcinoid Tumors by Immunohistochemical Investigation with Somatostatin Receptor Subtype 2 Antibodies¹

Departments of Internal Medicine, [E. T. J., A. G., K. Ö.], Clinical Chemistry [M. S.], and Oncology [J-E. W.], University Hospital, S-751 85 Uppsala, Sweden

We have shown previously that expression of mRNA for somatostatin receptor subtype 2 (sst₂) detected by in situ hybridization correlates to therapeutic outcome in patients with carcinoid tumors treated with somatostatin analogues. However, in situ hybridization is laborious and not practical in clinical routine work. We have, therefore, developed polyclonal antibodies directed against sst₂ that may be used for immunohistochemistry on tissue specimens. The staining is specific and is highly correlated to expression of mRNA for sst₂ (P < 0.01) as well as to tracer uptake at somatostatin receptor scintigraphy (P < 0.01). There is also a good correlation to the therapeutic response in carcinoid patients treated with somatostatin analogues (P < 0.05). Of 35 patients with carcinoid tumors included in this investigation, 25 stained positive with the antibodies. Twenty-two of these were investigated by somatostatin receptor scintigraphy and showed tracer uptake in metastases. An additional two patients that did not stain with the antibodies showed pathological uptake of the tracer in metastases, which might indicate binding to somatostatin receptor subtype 5. None of the 10 patients without positive immunostaining responded to somatostatin analogue treatment, whereas patients with a positive stain had a biochemical response or remained stable during treatment. Thus, these antibodies may be used to determine the presence of sst₂ in carcinoid tumors and to select patients suitable for somatostatin analogue treatment. The method is easily applicable in clinical practice.

¹ This work was supported by the Swedish Cancer Foundation, the Lions Fund for Cancer Research at Uppsala University Hospital, The Swedish Society of Medicine, and Söderbergs Foundation for Medical Research.

² To whom requests for reprints should be addressed, at Department of Internal Medicine, University Hospital, S0751 85 Uppsala, Sweden. Phone: 46-18-66 42 89; Fax: 46-18-51 01 33; E-mail: Eva.Tiensuu_Janson@medicin.uu.se.

Received 10/24/97. Accepted 3/27/98.

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