促甲状腺激素腺瘤的生长抑素受体表达与肿瘤侵袭性及相关性分析：系列报道

SSTRs expression and tumor invasiveness in TSH-secreting adenomas and correlation analysis： a series of reports

摘要:

目的 垂体促甲状腺激素腺瘤（thyroid stimulating hormone adenoma，TSHoma）的术后缓解率在不同研究间存在较大差异，本研究拟初步探究生长抑素受体（SSTRs）表达与TSH瘤形态特点、肿瘤侵袭性、术后缓解率间的相关性。方法 本研究回顾性分析了2015年10月至2019年4月于陆军军医大学第二附属医院诊断为10例TSH瘤患者的临床资料，9例患者接受了经鼻蝶或经颅垂体瘤切除术的。通过调阅磁共振成像图像详细评估肿瘤体积、侵袭性和T2加权信号强度重点区域（region of interests，ROI）信号强度。针对海绵窦侵袭性（cavernous sinus invasion score，CSIS）、蝶窦侵犯（sphenoid sinus invasion score，SSIS）、鞍上扩展（suprasellar extension score，SSES）进行评分，并计算累积评分（cumulative score，CS）。另外，对患者的垂体组织切片进行生长抑素受体（subtype-specific somatostatin receptors，SSTR）免疫组织化学染色，并用半定量免疫评分法进行评分。根据评分中位数，将患者分为高评分组（≥中位数）、低评分组（<中位数），比较临床资料间的差异。结果 10例TSH瘤患者年龄中位数为32.5岁，男女比为3∶2，均为大腺瘤，多向鞍上、鞍旁、海绵窦侵袭性生长，体积差异大（0.50~93.20 mL）。TSH瘤SSTRs染色评分呈现出如下趋势：SSTR2>SSTR5=SSTR3>SSTR1。进一步分析，高SSTR2评分组的TSH水平、肿瘤体积、knosp分级和侵袭性评分高于低评分组，而缓解率低于低评分组；与之相反的是，高SSTR5/SSTR2比值组的甲状腺激素水平、促甲状腺激素水平、肿瘤体积、knosp分级和海绵窦侵袭性评分低于低SSTR5/SSTR2组，而缓解率更高。遗憾的是，本研究中TSH瘤的侵袭性程度与肿瘤体积、甲状腺激素水平、TSH水平、ROI信号强度之间没有相关性。结论 SSTR2的表达量、SSTR5/SSTR2比值与侵袭性、生化水平有相关性，可能影响手术预后。

Abstract:

Objective The postoperative remission rate of thyroid-stimulating hormone（TSH）-secreting pituitary adenoma（TSHoma） varies greatly among different studies. This study was intended to preliminarily explore the correlation between the expression of somatostatin receptors（SSTRs） and the morphological characteristics，tumor invasiveness，and prognosis of TSHoma.Methods This study retrospectively analyzed the clinical data of 10 patients who were diagnosed with TSHoma in the Second Affiliated Hospital of Army Medical University from October 2015 to April 2019，and nine of them underwent transsphenoidal or transcranial pituitary tumor resection. By reviewing magnetic resonance imaging images，a detailed assessment of tumor volume，invasiveness，and T2 weighted signal intensity in key regions of interest（ROIs） was conducted. Cavernous sinus invasiveness，sphenoid sinus invasion，suprasellar expansion were scored，and their cumulative score was calculated. In addition，the pituitary tissue slices of patients were immunohistochemically stained with SSTRs and scored using the semi-quantitative immune scoring method. According to the median score，patients were divided into high score group（HSG）（≥median） and low score group （LSG）（<median），and the differences in clinical data between the two groups were evaluated.Results The median age of 10 patients with TSHoma was 32.5 years，and the male-to-female ratio was 3∶2. All of them had macroadenomas，with aggressive growth to the suprasellar，parasellar，and cavernous sinus and varied volumes（0.50-93.20 mL）. The SSTRs staining score of TSHoma showed the following trend：SSTR2>SSTR5=SSTR3>SSTR1. The further analysis showed that the TSH level，tumor volume，Knosp grade，and invasion score in the HSG of SSTR2 were higher than those in the LSG，while the remission rate was lower than that in the LSG. On the contrary，the thyroid hormone level，TSH level，tumor volume，Knosp grade，and cavernous sinus invasion score in the HSG of SSTR5/SSTR2 ratio were lower than those in the LSG，and the remission rate was higher than that in the LSG. Unfortunately，the invasiveness degree of TSHoma was not correlated with tumor volume，thyroid hormone level，TSH level，and signal intensity in the ROI.Conclusion The expression level of SSTR2，especially the SSTR5/SSTR2 ratio，is correlated with invasiveness and biochemical levels，which may affect the prognosis after surgery.