Division of Veterinary Surgery, Department of Veterinary Science, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo, Japan.
Domest Anim Endocrinol. 2011 Nov;41(4):207-13. doi: 10.1016/j.domaniend.2011.07.002. Epub 2011 Aug 23.
Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio ≤ 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean ± SD Ki-67 labeling index (LI) was 0.55% ± 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% ± 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% ± 2.2% and 10.9% ± 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries (P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas (P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI (r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI (r = 0.560, P = 0.03) and the MCM7 LI (r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors.
垂体依赖性库欣病（PDH）由垂体促肾上腺皮质激素腺瘤引起，是犬常见的内分泌疾病。垂体高度与脑面积的比值（P/B）用于评估垂体大小。P/B 比值>0.31 表示垂体增大，而 P/B 比值≤0.31 表示垂体未增大。本研究旨在探讨增殖标志物 Ki-67 和微小染色体维持蛋白 7（MCM7）在犬促肾上腺皮质激素腺瘤中的表达，这些腺瘤位于增大和未增大的垂体中，并评估它们与犬垂体促肾上腺皮质激素腺瘤大小的关系。通过双重免疫组织化学法检测了 15 例 PDH 犬切除的 ACTH 阳性肿瘤细胞中的 Ki-67 和 MCM7 的表达。P/B 比值非增大的促肾上腺皮质激素腺瘤的 Ki-67 标记指数（LI）平均值±标准差为 0.55%±0.59%，P/B 比值增大的腺瘤为 1.6%±0.6%。P/B 比值非增大的促肾上腺皮质激素腺瘤和 P/B 比值增大的腺瘤中的 MCM7 LI 分别为 2.9%±2.2%和 10.9%±3.7%。P/B 比值增大的腺瘤中的 Ki-67 LI 和 MCM7 LI 明显大于 P/B 比值非增大的腺瘤（P<0.01 和 P<0.01）。MCM7 LI 明显大于 Ki-67 LI（P<0.01）。Ki-67 LI 与 MCM7 LI 呈正相关（r=0.820，P<0.01），P/B 比值与 Ki-67 LI（r=0.560，P=0.03）和 MCM7 LI（r=0.854，P<0.01）呈正相关。总之，P/B 比值增大的犬促肾上腺皮质激素腺瘤比 P/B 比值未增大的腺瘤具有更大的增殖潜力。犬垂体促肾上腺皮质激素腺瘤中 MCM7 的表达明显大于 Ki-67 的表达。因此，MCM7 作为垂体肿瘤的增殖标志物可能优于 Ki-67。
