TY - JOUR
T1 - Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study.
AU - Iacovazzo, Donato
AU - Carlsen, Eivind
AU - Lugli, Francesca
AU - Chiloiro, Sabrina
AU - Piacentini, Serena
AU - Bianchi, Antonio
AU - Giampietro, Antonella
AU - Mormando, Marilda
AU - Clear, Andrew J.
AU - Doglietto, Francesco
AU - Anile, Carmelo
AU - Maira, Giulio
AU - Lauriola, Libero
AU - Rindi, Guido
AU - Roncaroli, Federico
AU - Pontecorvi, Alfredo
AU - Korbonits, Márta
AU - De Marinis Grasso, Laura
PY - 2016
Y1 - 2016
N2 - AIM:
To gather data regarding factors predicting responsiveness to pasireotide in acromegaly.
PATIENTS AND METHODS:
SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR.
RESULTS:
None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04).
CONCLUSION:
The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.
AB - AIM:
To gather data regarding factors predicting responsiveness to pasireotide in acromegaly.
PATIENTS AND METHODS:
SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR.
RESULTS:
None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04).
CONCLUSION:
The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.
KW - pituitary adenoma
KW - pituitary adenoma
UR - http://hdl.handle.net/10807/70868
U2 - 10.1530/EJE-15-0832
DO - 10.1530/EJE-15-0832
M3 - Article
SN - 1479-683X
VL - 174
SP - 241
EP - 250
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
ER -