Lee K T, Sheen P C
Department of Surgery, Kaohsiung Medical College Hospital, Taiwan.
Dig Dis Sci. 1999 Nov;44(11):2251-6. doi: 10.1023/a:1026604704029.
All cases of hepatolithiasis showed features of chronic proliferative cholangitis, and it has been speculated that the atypical glandular proliferation might be a precursor to overt cholangiocarcinoma. Proliferative cell nuclear antigen (PCNA) is a nuclear protein synthesized in the G1/S phase of the cell cycle and therefore is related to cell proliferative activity. In an attempt to assess the activity of cell proliferation of stone-containing intrahepatic bile ducts, we conducted a study using immunohistochemical staining with monoclonal antibody to score PCNA in intrahepatic bile ducts. Thirty patients (10 men, 20 women; mean age 52.4 years) having hepatolithiasis surgically resected were studied. Ten stone-free patients served as controls. All 40 specimens were immunostained for PCNA using PC 10 monoclonal antibody. PCNA of both stone-containing and stone-free intrahepatic bile ducts were assessed by counting positive staining nuclei per 500 cells and expressed as labeling index (LI), ie, percentage of positive nuclei to the total number of nuclei. The PCNA LI in stone-free intrahepatic bile ducts was generally low: 10.0+/-13.2%, 10.4+/-10.7% and 7.9+/-9.6% for extramural glands, intramural glands, and epithelial lining, respectively. In contrast, the PCNA LI for stone-containing intrahepatic bile ducts were significantly higher than those of controls (P < 0.001): 49.4+/-8.3%, 40.6+/-7.0% and 34.1+/-6.8% for extramural glands, intramural glands, and epithelial lining, respectively. The extramural glands had a significantly higher PCNA LI (P < 0.001) than the intramural glands and controls. Hyperplasia was found in all specimens, while dysplasia was found in six of 30 cases with hepatolithiasis. The dysplastic cells also had a higher PCNA LI (P < 0.001) than the hyperplastic cells and normal epithelium. Our findings showed that there is marked increase of activity of cell proliferation in stone-containing intrahepatic bile ducts. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results suggest that the high epithelial turnover in dysplastic cells and extramural glands had higher potential for proliferation and neoplastic transformation in long-standing untreated hepatolithiasis.
所有肝内胆管结石病例均表现出慢性增殖性胆管炎的特征，据推测，非典型腺性增生可能是显性胆管癌的前驱病变。增殖细胞核抗原（PCNA）是一种在细胞周期的G1/S期合成的核蛋白，因此与细胞增殖活性相关。为了评估含结石的肝内胆管的细胞增殖活性，我们进行了一项研究，使用单克隆抗体进行免疫组织化学染色，以对肝内胆管中的PCNA进行评分。对30例行手术切除肝内胆管结石的患者（男10例，女20例；平均年龄52.4岁）进行了研究。10例无结石患者作为对照。所有40份标本均使用PC 10单克隆抗体对PCNA进行免疫染色。通过计算每500个细胞中阳性染色核的数量来评估含结石和不含结石的肝内胆管的PCNA，并表示为标记指数（LI），即阳性核占核总数的百分比。不含结石的肝内胆管中的PCNA LI一般较低：壁外腺、壁内腺和上皮衬里的标记指数分别为10.0±13.2%、10.4±10.7%和7.9±9.6%。相比之下，含结石的肝内胆管的PCNA LI显著高于对照组（P<0.001）：壁外腺、壁内腺和上皮衬里的标记指数分别为49.4±8.3%、40.6±7.0%和34.1±6.8%。壁外腺的PCNA LI显著高于壁内腺和对照组（P<0.001）。所有标本均发现增生，而在30例肝内胆管结石病例中有6例发现发育异常。发育异常细胞的PCNA LI也高于增生细胞和正常上皮（P<0.001）。我们的研究结果表明，含结石的肝内胆管中细胞增殖活性显著增加。众所周知，增殖细胞中更容易发生基因突变。因此，我们的结果表明，在长期未经治疗的肝内胆管结石中，发育异常细胞和壁外腺中的高上皮更新具有更高的增殖和肿瘤转化潜力。
