Vidal S, Stefaneanu L, Kovacs K, Scheithauer B W
Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Pituitary. 1999 May;1(3-4):227-32. doi: 10.1023/a:1009990005835.
We studied the presence of von Hippel-Lindau protein (VHL-P) in 7 nontumorous pituitaries and 68 pituitary adenomas by immunocytochemistry using a polyclonal antibody which detects both normal and mutated forms. In nontumorous pituitary VHL-P was variable expressed in the cytoplasm of most adenohypophysial cells. In addition, weak diffuse staining was noted in the posterior lobe. Among the 53 VHL-P immunopositive adenomas (78%), 32 showed only cytoplasmic, 7 only nuclear, and 14 both cytoplasmic and nuclear immunoreactivity. In densely (8 cases) and sparsely (7 cases) granulated somatotroph adenomas nuclear and weak cytoplasmic immunoreactivity were common; all 4 sparsely granulated lactotroph adenomas had only moderate cytoplasmic immunostaining; all 7 functioning corticotroph adenomas presented intense cytoplasmic immunoreactivity and 4/7 showing nuclear immunostaining as well; all 3 silent subtype 1 adenomas were negative; 7 3/4 silent subtype 2 and 4/7 silent subtype 3 adenomas exhibited only cytoplasmic immunoreactivity; thyrotroph adenomas showed variable patterns from negative in 1/7, to only cytoplasmic in 2/7, nuclear alone in 2/7, or both in 2/7. Only weak, focal cytoplasmic immunoreactivity was noted in gonadotroph adenomas of female (2/4) and male (1/5) type. Lastly, all 4 null cell and 8 oncocytic adenomas showed moderate to intense cytoplasmic immunoreactivity. It can be concluded that the majority of pituitary adenomas express the VHL-P with variable distributions and intensity in different tumor types. The frequent localization of VHL-P in the nuclei of somatotroph adenomas, the least vascularized tumor type, suggests a possible inhibitory role of VHL-P in pituitary angiogenesis.
我们使用一种能检测正常和突变形式的多克隆抗体，通过免疫细胞化学方法研究了7个非肿瘤性垂体和68个垂体腺瘤中冯·希佩尔-林道蛋白（VHL-P）的存在情况。在非肿瘤性垂体中，VHL-P在大多数腺垂体细胞的细胞质中呈可变表达。此外，在后叶可见微弱的弥漫性染色。在53个VHL-P免疫阳性腺瘤（78%）中，32个仅显示细胞质免疫反应性，7个仅显示细胞核免疫反应性，14个同时显示细胞质和细胞核免疫反应性。在密集颗粒型（8例）和稀疏颗粒型（7例）生长激素细胞腺瘤中，细胞核和微弱的细胞质免疫反应性较为常见；所有4例稀疏颗粒型催乳素细胞腺瘤仅具有中等程度的细胞质免疫染色；所有7例功能性促肾上腺皮质激素细胞腺瘤均呈现强烈的细胞质免疫反应性，其中4/7也显示细胞核免疫染色；所有3例沉默型1型腺瘤均为阴性；7 3/4例沉默型2型和4/7例沉默型3型腺瘤仅表现出细胞质免疫反应性；促甲状腺激素细胞腺瘤呈现出多种模式，1/7为阴性，2/7仅为细胞质免疫反应性，2/7仅为细胞核免疫反应性，2/7为两者皆有。在女性（2/4）和男性（1/5）性腺激素细胞腺瘤中仅观察到微弱的、局灶性的细胞质免疫反应性。最后，所有4例无功能细胞腺瘤和8例嗜酸性细胞瘤均显示中等至强烈的细胞质免疫反应性。可以得出结论，大多数垂体腺瘤表达VHL-P，其在不同肿瘤类型中的分布和强度各不相同。VHL-P在血管化程度最低的生长激素细胞腺瘤细胞核中的频繁定位，提示VHL-P在垂体血管生成中可能具有抑制作用。
