Departments of Endocinology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Pituitary. 2012 Jun;15(2):166-73. doi: 10.1007/s11102-011-0300-9.
Patients with acromegaly have higher prevalence of colorectal neoplasms. The pathogenetic mechanism is still unclear and may be related to sustained increase in serum GH-IGF1. We aimed to evaluate the proliferative and apoptotic markers in samples of colonic mucosa obtained during screening colonoscopic biopsy from patients with acromegaly and study their relationship to serum IGF-1 and GH levels. The study subjects included 32 patients with acromegaly (4 female), 10 healthy controls (irritable bowel syndrome) and 10 positive controls (non-acromegalic colonic adenocarcinoma). Patients with acromegaly were divided into two groups, active disease (AD) and disease in remission (AR). Two biopsies each were obtained during colonoscopy from the right colon, transverse colon and rectosigmoid region. All the polyps were biopsied and subjected to histopathological examination. Immunohistochemistry for proliferation marker (Ki-67) and apoptotic markers (caspase-3 and TdT-Mediated dUTP Nick-End Labeling (TUNEL) was carried out in the histopathological samples. Indices of proliferation were significantly different in patients with acromegaly as compared to healthy controls. The mean Ki-67 positivity was 45.1 ± 17.7% in AD and 45.6 ± 23.1% in AR, as compared to 10 ± 5% in healthy controls. While none of the healthy controls had Ki-67 positivity beyond the lower third of crypts, among patients with acromegaly 12/32 (37.5%) had mid-third positivity (P = 0.000) and 15/32 (46.8%) had full length of crypt positively (P = 0.00). Immunostaining for caspase-3 was negative in patients with acromegaly and healthy controls. TUNEL was strongly positive in patients with colonic adenocarcinoma but not in healthy controls and patients with acromegaly. IGF-1 levels were higher in those with Ki-67 positivity in the superficial mucosa. Patients with acromegaly have increased proliferation of colonic epithelial cells. Elevated levels of serum IGF1 are associated with increase proliferation in the superficial crypt cells.
肢端肥大症患者结直肠肿瘤的患病率较高。其发病机制尚不清楚，可能与血清 GH-IGF1 的持续升高有关。我们旨在评估肢端肥大症患者筛查性结肠镜活检获得的结肠黏膜标本中的增殖和凋亡标志物，并研究其与血清 IGF-1 和 GH 水平的关系。研究对象包括 32 例肢端肥大症患者（4 名女性）、10 例健康对照者（肠易激综合征）和 10 例阳性对照者（非肢端肥大性结肠腺癌）。肢端肥大症患者分为活动期疾病（AD）和缓解期疾病（AR）两组。结肠镜检查时从右半结肠、横结肠和直肠乙状结肠区域各取 2 个活检标本。所有息肉均进行活检并进行组织病理学检查。对组织病理学标本进行增殖标志物（Ki-67）和凋亡标志物（caspase-3 和 TdT 介导的 dUTP 缺口末端标记（TUNEL）的免疫组化染色。与健康对照组相比，肢端肥大症患者的增殖指数明显不同。AD 患者的 Ki-67 阳性率为 45.1±17.7%，AR 患者为 45.6±23.1%，而健康对照组为 10±5%。虽然健康对照组中没有超过隐窝下三分之一的 Ki-67 阳性者，但在肢端肥大症患者中，有 12/32（37.5%）的患者中三分之一阳性（P=0.000），15/32（46.8%）的患者全长隐窝阳性（P=0.00）。肢端肥大症患者和健康对照组 caspase-3 的免疫染色均为阴性。TUNEL 在结肠腺癌患者中呈强阳性，但在健康对照组和肢端肥大症患者中则为阴性。在浅层黏膜中 Ki-67 阳性者的 IGF-1 水平较高。肢端肥大症患者的结肠上皮细胞增殖增加。血清 IGF1 水平升高与浅层隐窝细胞增殖增加有关。
