Background: Typing somatostatin receptor (SSTR) expression in neuroendocrine tumors (NETs) is of relevance to target an octreotide-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect SSTR is to date not paralleled by an accurate methodological setting and standardized interpretation of the results.
Objective: A multicentric study was designed to compare SSTR immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of NETs.
Design: After methodological setting by testing different SSTR antibodies, 107 cases of NETs with available OctreoScan data and pathological material (both surgical and preoperative) were retrospectively analyzed for SSTR type 2A immunohistochemical expression, and the results combined in a four grade scoring system (0 to 3) and compared with scintigraphic images and, whenever available, with the clinical response to somatostatin analogue treatment.
Results: Restricting positive cases to the presence of a membrane pattern of staining (proposed scores 2 and 3), an overall SSTR type 2A immunohistochemistry/OctreoScan agreement of 77% (Chi-square test P<0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of SSTR expression heterogeneity. Pure cytoplasmic staining showed poor correlation with OctreoScan images (54% concordance rate). In a pilot series, SSTR type 2A immunohistochemistry correlated with clinical response in 82% of 22 patients undergone to therapy with somatostatin analogs on the basis of a positive OctreoScan uptake.
Conclusions: A standardized scoring system for SSTR type 2A immunohistochemistry is proposed as a useful and reliable adjunct to OctreoScan in the clinical management of NET patients. A membranous SSTR type 2A staining well predicts clinical response to somatostatin analogue therapy and provides additional information on receptor distribution into a given tumor tissue and among primary and metastatic lesions.