Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2 expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs

摘要

Objectives: To evaluate somatostatin receptor 2A (SSTR2A) and dopamine receptor 2 (DR2) protein expression in somatotropinomas and to relate it to response to somatostatin analogues (SA). Design and patients: SSTR2A and DR2 expression was analyzed by immunohistochemistry in 88 somatotropinomas from patients submitted to either pre-surgical or adjuvant SA treatment. Tumors were scored according to percentage of immunostained cells: 0 (50). Relation between protein expression and response to SA was performed in 66 patients. Response to SA was assessed by percent IGF-I reduction, being considered as an IGF-I per cent reduction higher than 50. Disease control was also assessed (GH<1.0 ng/ml and normal IGF-I). Results: SSTR2A and DR2 were expressed in 100 and 98 of tumors, respectively. Biochemical response and disease control rates were 48 and 32, respectively. Median IGF-I percent reduction after 3 months of SA treatment was lower in the SSTR2A score 0 than in the scores 1 and 2 (p<0.001, both), and after 6 months in the score 0 than in the score 1 (p=0.001) and 2 (p<0.001). Biochemical response and disease control were associated with SSTR2 expression (p<0.001 and p=0.004, respectively). A negative predictive value for biochemical response of 100 was found when a SSTR2A expression <25of immunostained cells cut-off point was considered. No relation was found between DR2 expression and biochemical response and disease control. Conclusion: SSTR2A and DR2 are highly expressed in somatotropinomas. Low SSTR2A, but not DR2, expression is a negative predictive factor to response to SA.