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Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

¹ Endocrinology Section, ² Radiology Section, ³ Neurosurgery Section and ⁴ Pathology Section, ⁵ Hospital Universitário Clementino Fraga Filho, Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-913, Rio de Janeiro, Brazil⁶ Neurosurgery Section Hospital da Santa Casa de Misericórdia do Rio de Janeiro, Pontifícia Universidade Católica, 20020-022, Rio de Janeiro, Brazil⁷ Laboratório Diagnósticos da América S.A, 2271-040 and ⁸ Instituto Estadual de Diabetes e Endocrinologia Luis Capriglione, 20211-340, Rio de Janeiro, Brazil⁹ Clínica MultiImagem Ressonâncias, 22411-040 and ¹⁰ Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, 60612, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA

(Correspondence should be addressed to M R Gadelha who is now at Rua Nascimento Silva, 555/101, Ipanema, Rio de Janeiro 22421-020, Brazil; Email: mgadelha{at}hucff.ufrj.br)

Objective: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment.

Design and methods: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging).

Results: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046–5555), 2098 (194–23 954), 97 (0–460), 14 (0–29 480), and 0 (0–652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=–0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7–10) vs 0.3 (0.1–7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% – area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12).

Conclusions: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.