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.

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 (< 25%), 1 (25-50%), and 2 (> 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 < 25%of 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.

Validation of immunohistochemistry for somatostatin receptor subtype 2A in human somatotropinomas: comparison between quantitative real time RT-PCR and immunohistochemistry.

Somatostatin receptors subtype 2 (SSTR2) expression in somatotropinomas is recognized as a predictor of response to the currently available somatostatin analogs and may be analyzed, mainly, by quantitative RT-PCR or immunohistochemistry (IHC). The former has the advantages of a higher sensitivity and of being quantitative, while the latter, although semi-quantitative, evaluates protein expression and is routinely used in the evaluation of pituitary adenomas. We aimed to evaluate the SSTR2A protein expression in somatotropinomas and to compare it to our previous data regarding mRNA expression, assessed by quantitative real time RTPCR. Thirteen somatotropinomas were analyzed by IHC and the tumors were scored according to percent of immunostained cells: 0 (<25%), 1 (25-50%) and 2 (>50%). SSTR2A immunostaining was present in all but one somatotropinoma, 4 (31%) tumors were classified as score 0, 4 (31%) as score 1, and 5 (38%) as score 2. Median SSTR2 mRNA content was significantly different among the three IHC scores (p=0.036) and was lower in the score 0 than in the score 2 (p=0.016). The finding that there is a positive correlation between RT-PCR and IHC indicates that IHC can be applied in order to assess the SSTR2A content in somatotropinomas.