Immunohistochemical detection of somatostatin receptor types 1-5 in medullary carcinoma of the thyroid

BACKGROUND We have analysed the distribution of the five somatostatin recep tors (sst1-5) by immunohistochemistry in a large retrospective series of 51 medullary carcinoma of the thyroid (MCT) specimens and correlated the patt ern of sst expression with expression of somatostatin (SRIF) peptide, tumou r pathology and clinical outcome. MEASUREMENTS Immunohistochemistry was performed with rabbit polyclonal anti peptide antibodies directed against the extracellular domains or cytoplasmi c tail of human (h) sst1-5. SRIF immunoreactivity was investigated in paral lel paraffin sections. RESULTS Eighty-five percent of the tumours were positive for one or more ss t, localized to both tumour cells as well as surrounding peritumoural struc tures, especially blood vessels. Forty-nine percent of the tumours were pos itive for sst1, 43% for sst2, 47% for sst3, 4% for sst4, and 57% for sst5. Fifty-one percent of tumours expressed one or two sst subtypes; 33% were po sitive for three or more sst isoforms. All five sst receptors were detected in only two cases. Tumours expressing octreotide sensitive subtypes (sst2, 3,5) accounted for 75% of the series. 50% of the tumours co-expressed SRIF suggesting tumour cell regulation by endogenous SRIF via paracrine/autocrin e circuits. There was no correlation between sst1-5 expression and age, sex , tumour size or stage, histological type or clinical outcome. Simultaneous analysis of primary tumour and lymph node metastases revealed a similar pa ttern of sst immunoreactivity indicating that sst expression is not modifie d in the course of disease progression. CONCLUSIONS With the exception of sst4, medullary carcinoma of the thyroid display a rich but heterogeneous expression of sst subtypes. Immunohistoche mical typing of sst receptor expression using specific antireceptor antibod ies represents an ideal approach for characterizing sst subtype expression in medullary carcinoma of the thyroid for optimizing receptor targeted diag nosis and therapy with somatostatin analogs.