Behling Felix, Honegger Jürgen, Skardelly Marco, Gepfner-Tuma Irina, Tabatabai Ghazaleh, Tatagiba Marcos, Schittenhelm Jens
Department of Neurosurgery, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Germany.
Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Germany.
Int J Endocrinol. 2018 Dec 9;2018:1763735. doi: 10.1155/2018/1763735. eCollection 2018.
The development of somatostatin analogs for the treatment of pituitary Cushing's disease has been based on somatostatin receptor expression analyses of small cohorts of pituitary adenomas. Additionally, the classification of pituitary adenomas has recently changed. To enable progress with this treatment option, we assessed somatostatin receptors in a large cohort of corticotroph and other pituitary adenomas according to the new WHO classification of endocrine tumors. Paraffin-embedded tumor samples of 88 corticotroph pituitary adenomas and 30 nonadenomatous pituitary biopsies were analyzed after processing into tissue microarrays and immunohistochemical staining for SSTR 1, SSTR2A, SSTR3, SSTR4, and SSTR5. For comparison, 159 other noncorticotroph pituitary adenomas were analyzed. SSTR3 expression was higher in corticotroph adenomas compared to PIT-1-positive, gonadotroph, and nonfunctioning pituitary adenomas ( < 0.0001, = 0.0280, and < 0.0001, respectively). This was also the case for the expression of SSTR5 ( = 0.0003, < 0.0001, and < 0.0001, respectively). SSTR2A expression was higher compared to gonadotroph and nonfunctioning pituitary adenomas ( = 0.0217 and 0.0126, respectively) while PIT-1-positive adenomas showed even higher SSTR2A expression ( < 0.0001). SSTR2A and SSTR5 were both expressed higher in nonadenomatous pituitary biopsies than in pituitary adenomas ( = 0.0126 and = 0.0008, respectively). There are marked expression differences of SSTR1-5 as well as changes in expression in recurrent disease that need to be addressed when looking for other possible substances for the treatment of Cushing's disease. SSTR2A, SSTR3, and SSTR5 seem to be most suitable biomarkers for a targeted therapy with somatostatin analogs.
生长抑素类似物用于治疗垂体库欣病的研发基于对小队列垂体腺瘤的生长抑素受体表达分析。此外，垂体腺瘤的分类最近发生了变化。为推动这种治疗方案取得进展，我们根据世界卫生组织内分泌肿瘤新分类，在一大队列促肾上腺皮质激素细胞腺瘤和其他垂体腺瘤中评估了生长抑素受体。将88例促肾上腺皮质激素细胞垂体腺瘤的石蜡包埋肿瘤样本和30例非腺瘤性垂体活检样本制成组织微阵列并进行SSTR 1、SSTR2A、SSTR3、SSTR4和SSTR5免疫组化染色后进行分析。作为对照，对159例其他非促肾上腺皮质激素细胞垂体腺瘤进行了分析。与PIT-1阳性、促性腺激素细胞及无功能垂体腺瘤相比，促肾上腺皮质激素细胞腺瘤中SSTR3表达更高（分别为<0.0001、=0.0280和<0.0001）。SSTR5表达情况也是如此（分别为=0.0003、<0.0001和<0.0001）。与促性腺激素细胞及无功能垂体腺瘤相比，SSTR2A表达更高（分别为=0.0217和0.0126），而PIT-1阳性腺瘤的SSTR2A表达更高（<0.0001）。非腺瘤性垂体活检样本中SSTR2A和SSTR5的表达均高于垂体腺瘤（分别为=0.0126和=0.0008）。在寻找治疗库欣病的其他可能物质时，SSTR1 - 5存在显著表达差异以及复发疾病中的表达变化需要加以关注。SSTR2A、SSTR3和SSTR5似乎是生长抑素类似物靶向治疗最合适的生物标志物。
