Gonzalez Baldomero, Vargas Guadalupe, Ramirez Claudia, Asa Silvia, Cheng Sonia, Sandoval Carolina, Mercado Moises
Endocrine Service and Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional, S.XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
University Health Network and The Ontario Cancer Center, Toronto, Ontario, Canada.
Endocrinol Nutr. 2014 Dec;61(10):523-30. doi: 10.1016/j.endonu.2014.05.006. Epub 2014 Jul 5.
To evaluate expression of somatostatin receptor subtypes 2 and 5 (SSTR 2 and 5) by RT/PCR and immunohistochemistry (IHC) in GH-secreting adenomas, seeking correlations with response to octreotide.
SSTR2 and 5 expression was tested by IHC (n=37), RT/PCR (n=36) or both (n=13) in GH-secreting adenomas from 60 patients with acromegaly who had undergone pituitary surgery; 36 had been treated preoperatively with octreotide LAR for 3-6 months, and were categorized as responders (achievement of GH <2.5ng/mL and a normal age-adjusted IGF-1), partial responders (GH and IGF-1 reduction >50% and >30%, respectively) or non-responders. IHC was performed on a tissue microarray using specific antibodies directed to the carboxyl terminus of SSTR2 and 5.
SSTR5 was the predominantly expressed receptor subtype by both IHC and RT/PCR in all tumors tested, regardless of whether they came from octreotide-naïve, octreotide-responsive, or octreotide-resistant patients. Immunostaining was concentrated in the cytoplasm. Neither SSTR2 nor SSTR5 expression correlated with baseline or post-octreotide GH or IGF-1 levels or tumor volume by either method. The agreement rate between RT/PCR and IHC was 77% in all 13 adenomas in which both methods were used.
Expression of these receptors does not guarantee an adequate response to somatostatin analogs; other functional aspects of this interaction, such as receptor homo- and heterodimerization, and the resulting signaling cascade, probably play a role in determining whether a patient will respond or not to these agents.
通过逆转录聚合酶链反应（RT/PCR）和免疫组织化学（IHC）评估生长激素分泌性腺瘤中生长抑素受体亚型2和5（SSTR 2和5）的表达，寻找其与奥曲肽反应的相关性。
对60例接受垂体手术的肢端肥大症患者的生长激素分泌性腺瘤进行检测，采用免疫组织化学法（n=37）、RT/PCR法（n=36）或两种方法同时使用（n=13）检测SSTR2和5的表达；36例患者术前接受奥曲肽长效释放制剂治疗3至6个月，并分为反应者（生长激素<2.5ng/mL且年龄校正后的胰岛素样生长因子-1正常）、部分反应者（生长激素和胰岛素样生长因子-1分别降低>50%和>30%）或无反应者。使用针对SSTR2和5羧基末端的特异性抗体在组织芯片上进行免疫组织化学检测。
在所有检测的肿瘤中，无论其来自未使用过奥曲肽、对奥曲肽有反应或对奥曲肽耐药的患者，SSTR5都是通过免疫组织化学和RT/PCR主要表达的受体亚型。免疫染色集中在细胞质中。两种方法检测，SSTR2和SSTR5的表达均与基线或奥曲肽治疗后的生长激素或胰岛素样生长因子-1水平或肿瘤体积无关。在同时使用两种方法检测的13例腺瘤中，RT/PCR与免疫组织化学的符合率为77%。
这些受体的表达并不能保证对生长抑素类似物有充分反应；这种相互作用的其他功能方面，如受体同源和异源二聚化以及由此产生的信号级联反应，可能在决定患者是否对这些药物有反应中起作用。
