Galitskiĭ M V, Khomeriki S G, Nikiforov P A
Eksp Klin Gastroenterol. 2009(5):28-32.
The cholecystectomy results in change of cholic acids flow into intestine. Permanent type of the bile flow provokes the increase of proliferation of colic epithelial cells and increases the risk for development of right-sided colorectal tumors. Meanwhile morphological features of colorectal tumors at the patients with cholecystectomy are still remaining to be clarified. The goal of the study was to investigate immunohistochemical markers of proliferation and apoptosis in colorectal adenomas and adenocarcinomas at the patients with cholecystectomy. Fifty patients (40 with retained function of gallbladder and 10 patients with cholecystectomy) histologically diagnosed as proximal colon adenoma or adenocarcinoma were included into the study. Colonoscopic biopsies have been taken from the lesion in cancer patients, and colonoscopic polypectomy has been performed for adenomas. In addition, biopsies have been taken from the adjacent healthy colon mucosa at least 5 cm from the lesion in each patient. 83 tumors and 49 samples of mucosa were immunostained with monoclonal mouse anti-human p53 protein (Dako) and monoclonal mouse anti-human Ki-67 antigen (Novocastra). The index of Ki-67 expression in healthy colon mucosa at the patients with cholecystectomy was 37,5 +/- 1,8% (p < 0,05) as compared to 31,36 +/- 1,9 at the patients without cholecystectomy. No significant difference was detected in the comparison of Ki-67 expression levels between the healthy mucosa and adenomas at the patients with cholecystectomy 43,4 +/- 3,45 (p > 0,05), but more prominent increase was revealed in adenocarcinomas 64,33 +/- 7,67% (p < 0,01). Protein p53 expression in healthy mucosa at the patients with a cholecystectomy was at the same level as at the patients without cholecystectomy (37%). At the patients without cholecystectomy the frequency of revealing p53 in adenomas does not vary, compared with healthy mucosa, however in adenocarcinomas p53 was not revealed at none case. As a contrast, in group of the patients with cholecystectomy the frequency of revealing p53 in adenomas is considerably increased (up to 80%), and even in adenocarcinomas, p53 was revealed in 30,8% of cases. Thus, in benign colorectal tumors at the patients with retained function of gallbladder intensifying of epithelial cells proliferation is not accompanied with intensifying of apoptosis, and in malignant tumors a complete supression of apoptosis is observed. At the patients with a cholecystectomy, the increase of proliferative activity is accompanied by increased apoptosis in adenomas and maintained apoptosis in adenocarcinomas. The retaining of apoptosis in colorectal tumors compensates intensive proliferative activity with expectation of better prognosis.
胆囊切除术会导致胆汁酸流入肠道的情况发生改变。永久性胆汁流动类型会促使结肠上皮细胞增殖增加，并增加右侧结直肠肿瘤发生的风险。与此同时，胆囊切除术后患者结直肠肿瘤的形态学特征仍有待阐明。本研究的目的是调查胆囊切除术后患者结直肠腺瘤和腺癌中增殖和凋亡的免疫组化标志物。50例经组织学诊断为近端结肠腺瘤或腺癌的患者（40例胆囊功能保留患者和10例胆囊切除患者）被纳入研究。对癌症患者的病变部位进行了结肠镜活检，对腺瘤进行了结肠镜息肉切除术。此外，在每位患者距病变至少5厘米的相邻健康结肠黏膜处取活检。用小鼠抗人p53蛋白单克隆抗体（Dako）和小鼠抗人Ki-67抗原单克隆抗体（Novocastra）对83个肿瘤和49个黏膜样本进行免疫染色。胆囊切除术后患者健康结肠黏膜中Ki-67表达指数为37.5±1.8%（p<0.05），而未进行胆囊切除术的患者为31.36±1.9%。胆囊切除术后患者健康黏膜与腺瘤之间Ki-67表达水平比较无显著差异（43.4±3.45，p>0.05），但腺癌中Ki-67表达明显升高（64.33±7.67%，p<0.01）。胆囊切除术后患者健康黏膜中p53蛋白表达与未进行胆囊切除术的患者处于同一水平（37%）。在未进行胆囊切除术的患者中，腺瘤中p53的检出频率与健康黏膜相比无变化，然而在腺癌中无一例检出p53。相反，在胆囊切除术后患者组中，腺瘤中p53的检出频率显著增加（高达80%），甚至在腺癌中，30.8%的病例中检出p53。因此，在胆囊功能保留患者的良性结直肠肿瘤中，上皮细胞增殖加剧但凋亡未加剧，而在恶性肿瘤中观察到凋亡完全受抑制。在胆囊切除术后患者中，腺瘤中增殖活性增加伴随着凋亡增加，腺癌中凋亡维持。结直肠肿瘤中凋亡的保留补偿了强烈的增殖活性，预期预后较好。
