The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma
The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma
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DOI：
10.1111/j.1365-2265.2007.03065.x
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发表时间：
2008-03-01
影响因子：
3.2
通讯作者：
Bollerslev, Jens
中科院分区：
文献类型：
--
作者：
Fougner, Stine L.;Borota, Olivera Casar;Bollerslev, Jens
目的生长抑素受体亚型2（SSTR 2）表达降低是奥曲肽治疗肢端肥大症疗效差的一种解释，但SSTR 2 mRNA水平与奥曲肽疗效相关的研究存在矛盾。一些研究发现生长抑素类似物在G蛋白α亚基（Gs α）突变（gsp癌基因）阳性腺瘤中有更好的反应。本研究的目的是确定腺瘤SSTR 2a蛋白表达和gsp状态在一个大的肢端肥大症患者组，并将其与奥曲肽的临床效果。所有患者均行经蝶窦手术，23例患者术前经奥曲肽治疗。方法采用免疫组化和Western blot分析法检测腺瘤SSTR 2a表达，并测定gsp状态。一个急性奥曲肽试验进行，并在IGF-1水平的变化后，6个月的术前奥曲肽treatment recorded.Results的急性奥曲肽反应在非预处理的患者和术前长期奥曲肽反应显着更好的腺瘤患者含有很大比例的细胞，染色阳性SSTR 2a免疫组化。然而，通过Western blot评估的SSTR 2a蛋白水平与奥曲肽反应不相关。术前治疗组的SSTR 2a蛋白水平较低，腺瘤较少，阳性染色细胞百分比较高。结论奥曲肽的临床疗效与SSTR 2a蛋白表达水平无关，而与SSTR 2a免疫组化染色阳性细胞的比例有关。在奥曲肽治疗期间可能存在SSTR 2a的下调。
Objective Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G-protein alpha subunit (Gs alpha) mutation (gsp oncogene)-positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide.Patients Seventy-one patients were included. All underwent transsphenoidal surgery, 23 patients after preoperative octreotide treatment.Measurements The adenoma SSTR2a expression was examined by immunohistochemistry and Western blot analysis, and gsp status determined. An acute octreotide test was performed, and the change in IGF-1 level after 6 months preoperative octreotide treatment was recorded.Results The acute octreotide response in non-pretreated patients and the preoperative long-term octreotide response were significantly better in patients with adenomas containing a large proportion of cells that stained positively for SSTR2a by immunohistochemistry. However, the SSTR2a protein level assessed by Western blot did not correlate with the octreotide response. The preoperatively treated group had lower SSTR2a protein levels and fewer adenomas with a large percentage of positively stained cells. The gsp oncogene was detected in 43% of the adenomas but did not correlate to the octreotide response.Conclusion The clinical effect of octreotide correlates with the proportion of cells positive for SSTR2a in immunohistochemical staining, rather than the adenoma SSTR2a protein level. There may be a down-regulation of SSTR2a during octreotide treatment.