CLINICAL SIGNIFICANCE OF CELLULAR EXPRESSION OF KL-6 MUCIN IN CHOLANGIOCRCINOMA

胆管癌（CC）患者的预后比肝细胞癌（HCC）患者尤其差，这是由于许多病例中胆管癌的诊断困难。因此，寻找一种有效的肿瘤标志物对CC进行早期诊断和预后评估具有重要意义。在本研究中，我们旨在通过免疫组织化学和血清学分析阐明KL-6粘蛋白在CC患者中的意义。组织化学分析显示，仅在CC组织中检测到KL-6粘蛋白阳性染色，而在所有肝癌组织的HCC组织和正常肝区均未检测到KL-6粘蛋白阳性染色。血清学分析显示，与健康人、HCC患者和转移性肝癌患者相比，CC患者血清KL-6粘蛋白水平升高（P<0.0001），并可将临界值设置为248 U/mL与其他肝癌患者区分。提示KL-6粘蛋白可用于CC患者的组织化学检测和血清学鉴别。此外，转移性肝癌组织的免疫组化分析显示，所有组织均阳性表达KL-6粘蛋白，但KL-6的表达特征与CC组织不同，血清中KL-6粘蛋白水平也不同。此外，对多种结肠癌细胞系的实验表明，KL-6粘蛋白的定位与癌细胞形态和转移潜能等癌症行为有显著关系。本研究表明，KL-6是CC诊断和阐明各种胃肠道肿瘤行为的前瞻性工具。

Patients with cholangiocarcinoma (CC) has particularly worse prognosis than those with hepatocellular carcinoma (HCC), which is due to the difficulty of the diagnosis of CC in many cases. Thus, it is important to develop an effective tumor marker that can diagnosis CC in early phase and estimate patients' prognosis. In this study, we aimed to elucidate significance of KL-6 mucin in CC patients by immunohistochemical and seralogical analyses. The histochemical analysis showed that positive staining of KL-6 mucin was detected only in CC tissues but not in HCC tissues and normal liver regions of all liver cancer tissues. Serological analysis showed serum KL-6 mucin level was elevated in CC patients compared with healthy individuals, HCC patients and metastatic liver cancer patients (P<0.0001) and that CC patients were able to be discrminate from other liver cancer patients by setting a cut-off value at 248 U/mL. These results indicated that KL-6 mucin might be useful in the histochemical detection and serological discrimination of CC patients. Furthermore, the immunohistochemical analysis of metastatic liver cancer tissues displayed that all tissues were positive for KL-6 mucin, but the characteristics of KL-6 expression is not the same as CC tissues as well as serum KL-6 mucin level. Moreover, experiment using various kinds of colon cancer lines showed that the localization of KL-6 mucin was significantly related to the cancer behavior such as cancer cell morphology and metastatic potential. The present study indicates that KL-6 is prospective tool for CC diagnosis and elucidation of various gastrointestinal cancer behaviors.