Somatostatin (SS) receptor status was investigated in the
tumor tissues from 62 patients with
carcinoid tumors and 15 patients with
islet cell carcinomas using receptor autoradiography techniques with two different iodinated
somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]
somatostatin-28 and a
somatostatin octapeptide, Tyr3-octreotide. The
carcinoid tumors were either primaries (n = 32) or
metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62
carcinoid patients had SS receptor-positive
tumors (87%). All 15
islet cell carcinoma patients had positive
tumors (4 primaries, 11
metastases), i.e., 3
vipomas, 3
insulinomas, 2
glucagonomas, 1
gastrinoma, 2 polyfunctional
tumors, and 4 nonfunctioning
tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the
tumors, the receptors were densely distributed and were always homogeneously found in the whole
tumor. All except two
tumors were labeled with both radioligands. Multiple liver
metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver
metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative
carcinoids were mainly bronchial
carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All
tumors except one from patients pretreated with
octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of
carcinoids or
islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (
hormone inhibition) to
octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary
tumors of both
carcinoids and
islet cell carcinomas, (b) their presence in
metastases as well, (c) their continuous expression even during long term
octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for
octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in
carcinoids and
islet cell carcinomas.