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 presurgical or adjuvant SA treatment. Tumors were scored according to percent 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 percent reduction higher than 50%. It was also assessed disease control (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.
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.
MINUTO, FRANCESCO;FERONE, DIEGO;
2013-01-01
Abstract
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 presurgical or adjuvant SA treatment. Tumors were scored according to percent 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 percent reduction higher than 50%. It was also assessed disease control (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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.