Immunohistochemical Detection of Somatostatin Receptor (SSTR) Subtypes 2A and 5 in Pituitary Adenoma from Acromegalic Patients: Good Correlation with Preoperative Response to Octreotide

Takei, Mao; Suzuki, Masanori; Kajiya, Hanako; Ishii, Yudo; Tahara, Shigeyuki; Miyakoshi, Tatsuyoshi; Egashira, Noboru; Takekoshi, Susumu; Sanno, Naoko; Teramoto, Akira; Osamura, R. Yoshiyuki

doi:10.1007/s12022-007-9004-0

Cited by 35 publications

(26 citation statements)

References 60 publications

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“…It could be argued that cytoplasmic expression represents an unspecific finding and these cases could be grouped with tumours not expressing SSTRs, restricting then the positivity to membrane-associated staining. These results are in line with previous studies where SSTR2a expression was investigated using IHC (12,13,14,15,16,17). These studies employed different scoring systems, mainly accounting for the intensity and the extent of the staining.…”

Section: European Journal Of Endocrinologysupporting

confidence: 91%

“…Numerous factors are associated with resistance to first-generation SSAs (10), including reduced expression of SSTR2a (11,12,13,14,15,16,17,18), sparsely granulated adenoma subtype (19,20,21,22) and a higher Ki-67 proliferation index (23,24). Adenomas that occur in patients with AIP mutations and AIP mutation-negative sporadic somatotroph adenomas with reduced AIP expression show increased invasiveness (25,26,27,28) and are frequently resistant to first generation SSAs (29).…”

Section: Introductionmentioning

confidence: 99%

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Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Iacovazzo

Carlsen²,

Lugli

et al. 2016

European Journal of Endocrinology

139

109

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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 firstgeneration SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (PZ0.04). 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 (PZ0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; PZ0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; PZ0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; PZ0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; PZ0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; PZ0.04). 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.

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Section: European Journal Of Endocrinologysupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Iacovazzo

Carlsen²,

Lugli

et al. 2016

European Journal of Endocrinology

139

109

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“…Germany), and dopamine D2 receptor (DRD2). Semiquantitative scoring for the SSTRs [22,23] and DRD2 [24] protein was performed by the experienced pathologist as previously described.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…We evaluated the immunoreactivity of somatostatin receptor (SSTR) 2, 5, and dopamine D2 receptor (DRD2), which were defined by the ratio of positive cells as previously described [22][23][24]. SSTR2 immunoreactivity was scored as (++) in patient 7 and as (+) in patient 2, 3, and 8 (Fig.…”

Section: Sstr and Drd2 Expression In The Tumormentioning

confidence: 99%

Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: a retrospective clinical study and review of the literature

et al. 2013

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“…Patients bearing densely granulated somatotropinomas on electron microscopy respond better to SA therapy than patients with sparsely granulated tumors (17). Immunohistochemical detection of somatostatin receptor subtype 2 (SSTR2) correlates positively with percent GH reduction on acute test and IGF-I after 6 months of treatment (18,19). When molecular analysis of the ressected tumor is possible, the presence of the gsp oncogene seems to be indicative of a good response to SA treatment (20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

Neto

Taboada

Gadelha

2008

Arq Bras Endocrinol Metab

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We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR ® therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR ® therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA -SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent noncurative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/ mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR ® therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA -SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be confl icting as predictors of octreotide LAR ® responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients. RESUMO Expressão dos Receptores da Somatostatina Subtipos 2 e 5 e do Receptor da Dopamina tipo 2 e gsp Status como Preditores de Resposta ao Octreotide LAR® na Acromegalia.Apresentamos dois pacientes acromegálicos nos quais dados clínicos e moleculares são discutidos quanto à sua capacidade de predizer a resposta a longo prazo ao tratamento com octreotide LAR ® . Relato dos casos: Paciente 1: Feminina, 36 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 133 ng/mL e 181% acima do limite superior do valor de referência (LSVR), respectivamente. GH durante o teste agudo com octreotide subcutâneo diminuiu de 133 para 13 ng/mL. Foi iniciado tratamento primário com octreotide LAR ® (20 mg q28 dias) e a paciente alcançou os parâmetros bioquímicos de controle de doença depois de seis meses. Análise molecular do tumor: gsp +; análise quantitativa do mRNA de SSTR (receptores de somatostatina) e DR (receptor de dopamina) -SSTR2 23.954; SSTR5 2.407; DR2 total 17.016 có-pias. Paciente 2: Masculino, 38 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 120 ng/mL e 114% LSVR, respectivamente. Paciente foi sub-

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Immunohistochemical Detection of Somatostatin Receptor (SSTR) Subtypes 2A and 5 in Pituitary Adenoma from Acromegalic Patients: Good Correlation with Preoperative Response to Octreotide

Abstract: Immunohistochemistry for SSTR2A in pathology specimens from acromegalic patients enabled selection of those experiencing clinical benefit from octreotide. Therefore, performing immunohistochemistry for detection of SSTR2A is recommended for all specimens obtained by surgery.

Cited by 35 publications

References 60 publications

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: a retrospective clinical study and review of the literature

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

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