多巴胺D_2受体在垂体腺瘤中的表达及临床意义

Expression and clinical significance of D_2 receptor in pituitary adenomas

目的垂体腺瘤约占颅内原发性肿瘤的10%-15%。多巴胺受体激动剂是治疗泌乳素（PRL）腺瘤的一线药物,并且对其它垂体腺瘤类型部分病例有效。研究表明：多巴胺受体激动剂是通过结合并激活多巴胺D2受体（D2R）发挥作用。本研究通过免疫组化的方法检测垂体腺瘤中D2R的表达情况。方法本研究所用197例垂体腺瘤标本均来自南京军区南京总医院神经外科手术病例。采用SP免疫组织化学染色法检测垂体腺瘤中D2R的表达。在光学显微镜下分析D2R在细胞中的定位及用半定量方法分析标本中阳性细胞的表达情况。免疫反应低表达定义为最终评分≤2分,高表达定义最终评分为〉2分。结果 D2R定位于垂体腺瘤细胞胞浆。D2R在垂体腺瘤细胞中高表达率为65%,在PRL腺瘤和生长激素（GH）腺瘤的高表达率最高分别为为92.9%、90%;无功能性腺瘤（NFPA）D2R高表达率最低,仅为37.1%。D2R高表达率和垂体腺瘤的类型相关,与患者性别、肿瘤大小、肿瘤质地、侵袭性、是否复发或是否服用溴隐亭无显著相关性。结论 PRL腺瘤和GH腺瘤中D2R表达量高,适合多巴胺受体激动剂治疗;NFPA中D2R表达量低,不适合多巴胺受体激动剂治疗。

Objective Pituitary tumors represent 10% - 15% of primary intracranial neoplasms.Dopamine agonists are the first line therapy for prolactinomas,which are also effective in some cases of other subtypes. It had been showed that dopamine agonists inhibit prolactin secretion by binding to and activating dopamine D2receptors（ D2R）. The aim of the current study is to evaluate the expression of D2R using immunohistochemistry in pituitary adenomas. Methods All patients with pituitary adenomas received pituitary surgery in the Department of Neurosurgery of Jinling Hospital. The expression of D2R was detected by immunohistochemical SP method in 197 cases. D2R was analyzed semiquantitatively under a light microscope. Low expression was defined as final score ≤2 score and high expression was defined as final score 〉2 scores. Results The positive reactions were found in cell cytoplasm. The D2R high expression rate was 65%. The high expression rate was found to be highest in prolactinomas（ 92. 9%）,followed by somatotropinomas（ 90%）. The lowest rate was observed in nonfunctioning pituitary adenomas（ 37. 1%）.The high expression rate of D2R in different subtypes of pituitary adenomas was statistically significant.However,the difference was not found regarding patient＇s sex,tumor size,invasiveness,recurrence,texture and whether bromocriptine was used or not. Conclusion Prolactinomas and somatotropinomas show higher expression of D2R,which supports the results that prolactinomas and somatotropinomas are more responsible for dopamine agonists. Nonfunctioning pituitary adenomas exhibit lowest D2R expression and may be not suitable for dopamine agonists therapy.