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

Eur J Endocrinol. 2008 Mar;158(3):295-303. doi: 10.1530/EJE-07-0562.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy
  • Acromegaly / physiopathology
  • Adenoma / drug therapy*
  • Adenoma / metabolism
  • Adenoma / pathology*
  • Adult
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Female
  • Growth Hormone / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Octreotide / therapeutic use*
  • Pituitary Neoplasms / drug therapy*
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology*
  • Predictive Value of Tests
  • RNA, Messenger / metabolism
  • Receptors, Somatostatin / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Somatostatin
  • somatostatin receptor 3
  • somatostatin receptor subtype-4
  • somatostatin receptor type 1
  • somatostatin receptor 5
  • Growth Hormone
  • somatostatin receptor 2
  • Octreotide