Research Institute for Internal Medicine, University of Oslo, Norway.
Clin Endocrinol (Oxf). 2012 Jan;76(1):96-102. doi: 10.1111/j.1365-2265.2011.04163.x.
Somatotroph adenomas have been classified into densely granulated (DG) and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp oncogenes are activating mutations in the Gsα subunit gene, found in approximately 40% of somatotroph adenomas.
To explore granulation pattern and presence of gsp oncogene in acromegaly with correlations to clinical and biochemical variables and to the effect of treatment with somatostatin analogues (SA), as well as to describe granulation pattern in adenomas with and without SA pretreatment.
DESIGN/SETTINGS/PATIENTS: Seventy-eight patients with active acromegaly were included. Long-term SA efficacy was evaluated in 29 patients treated preoperatively and in ten treated postoperatively. Granulation pattern was examined, as were immunohistochemical analyses for E-cadherin and SSTR2a. Protein levels of E-cadherin and SSTR2a were measured (Western blot). Gsp mutation analysis was available for 74 adenomas.
DG adenomas and the transitional group had higher serum levels of IGF-1 per tumour volume than SG (P = 0·009; P = 0·005). Acute and long-term SA responses were lower in SG (P = 0·001; P = 0·043). No correlation between gsp mutation and granulation was found, and no difference in granulation pattern according to preoperative SA treatment was demonstrated. A significant correlation between granulation and E-cadherin was found, where SG had lowest immunohistochemical expression, substantiated by protein levels, and a highly significant gradient was observed from DG, through the transitional group, to SG.
Densely granulated adenomas were highly responsive to somatostatin analogues in contrast to SG adenomas. The transitional group behaved clinically more like DG adenomas. However, based on E-cadherin, a marker of dedifferentiation, the transitional group seemed to be a true intermediate.
生长激素腺瘤可分为致密颗粒型（DG）和稀疏颗粒型（SG）肿瘤，以及一种过渡型、中间型。Gsp 癌基因是在大约 40%的生长激素腺瘤中发现的 Gsα 亚单位基因的激活突变。
探讨肢端肥大症中颗粒形成模式和 gsp 癌基因的存在，并与临床和生化变量以及生长抑素类似物（SA）治疗的效果相关，以及描述 SA 预处理前后腺瘤的颗粒形成模式。
设计/设置/患者：纳入 78 例活动性肢端肥大症患者。对 29 例术前和 10 例术后接受 SA 治疗的患者进行了长期 SA 疗效评估。检查了颗粒形成模式，并进行了 E-钙黏蛋白和 SSTR2a 的免疫组织化学分析。测量了 E-钙黏蛋白和 SSTR2a 的蛋白水平（Western blot）。可获得 74 个腺瘤的 gsp 突变分析。
DG 腺瘤和过渡组的 IGF-1 血清水平/肿瘤体积高于 SG（P = 0.009；P = 0.005）。SG 的急性和长期 SA 反应较低（P = 0.001；P = 0.043）。未发现 gsp 突变与颗粒形成之间存在相关性，也未发现根据术前 SA 治疗的颗粒形成模式存在差异。发现颗粒形成与 E-钙黏蛋白之间存在显著相关性，其中 SG 的免疫组织化学表达最低，蛋白水平也证实了这一点，从 DG 到过渡组到 SG 观察到高度显著的梯度。
与 SG 腺瘤相比，致密颗粒型腺瘤对生长抑素类似物高度敏感。过渡组在临床上更类似于 DG 腺瘤。然而，基于 E-钙黏蛋白，一种去分化的标志物，过渡组似乎是真正的中间型。
