影响肝内胆管细胞癌手术效果的有关因素(附17例报告)

目的　探讨肝内胆管细胞癌的生物学特征及手术方式等因素对手术切除效果的影响。方法　总结 1987年至 1997年收治手术切除 17例肝内胆管癌的临床资料和经验。结果　左半肝切除 6例 ,左半肝扩大切除 3例 ,右半肝切除 3例 ,右半肝扩大切除 1例 ,肝Ⅳb、Ⅴ、Ⅵ段横行切除 2例。术后 1年、3年、5年生存率为 6 4 7%、35 3 %、11 8%。结论　肝内胆管癌的浸润、转移方式及与之相适应的手术方式是影响手术效果的重要因素     

Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is ranked as one of the top five causes of cancer-related deaths. ICCin Thai patients is associated with infection with the liver fluke, Opisthorchis viverrini, but the molecular basis fordevelopment remains unclear. The present study employed a microarray approach to compare gene expressionprofiles of ICCs and normal liver tissues from the same patients residing in Northeast Thailand, a region witha high prevalence of liver fluke infection. In ICC samples, 2,821 and 1,361 genes were found to be significantlyup- and down-regulated respectively (unpaired t-test, p<0.05; fold-change ≥2.0). For validation of the microarrayresults, 7 up-regulated genes (FXYD3, GPRC5A, CEACAM5, MUC13, EPCAM, TMC5, and EHF) and 3 downregulatedgenes (CPS1, TAT, and ITIH1) were selected for confirmation using quantitative RT-PCR, resultingin 100% agreement. The metallothionine heavy metal pathway contains the highest percentage of genes withstatistically significant changes in expression. This study provides exon-level expression profiles in ICC thatshould be fruitful in identifying novel genetic markers for classifying and possibly early diagnosis of this highlyfatal type of cholangiocarcinoma.     

肝内胆管癌手术治疗的预后影响因素分析

目的 探讨肝内胆管癌患者手术治疗后炎症细胞分布与预后的相关性及影响预后的相关因素.方法 纳入行手术根除治疗的肝内胆管癌患者60例,对患者的详细就诊资料、CD15、CD68炎性相关性因素及生存资料等进行相关性分析.结果 分化程度、肿瘤复发、TNM分期、CA199、术中输血、手术方式、肿瘤和手术部位、术前转氨酶水平的情况是影响胆管癌预后总生存时间的独立危险因素.炎症相关因子CD15、CD68的表达与患者的总生存时间有关(P<0.05).结论 肝内胆管癌手术治疗的预后与肿瘤的分化程度、肿瘤复发、TNM分期、CA199、术中输血、手术方式、肿瘤和手术部位、术前转氨酶水平具有相关性,局部的炎症状态CD15高表达、CD68低表达是影响胆管癌患者总生存时间的独立危险因素.     

肝内胆管细胞癌根治术的预后因素分析

[目的]分析影响肝内胆管细胞癌(IHC)根治术预后的因素.[方法]回顾性分析82例IHC患者的临床及病理资料,阅读病理切片,寻找显微镜下是否存在微转移灶.对所有患者进行定期随访,并行生存分析.[结果] 82例IHC手术切除标本中,53例(64.6％)显微镜下可见微转移灶.存在微转移灶、γ-谷氨酰转肽酶(γ-GT)高、癌胚抗原(CEA)增高及有肝内结石或血吸虫等慢性肝病史是IHC的独立预后因素.[结论]镜下存在微转移灶、CEA增高、慢性肝病史、γ-GT升高是根治性切除后的IHC独立不良预后因素,根治术后应积极治疗.     

Expression of Matrix Metalloproteinase 2 and Extracellular Matrix Metalloproteinase Inducer are Unfavorable Postoperative Prognostic Factors in Intrahepatic Cholangiocarcinoma

Many investigators have indicated that overexpression and amplification of matrix metalloproteinase 2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) are independent prognostic factors for primary tumors. We studied expression of them in tissues from intrahepatic cholangiocarcinoma (IHCCA) and normal bile ducts, and discussed the occurrence and development of IHCCA. Another goal was to explore possible association of MMP-2 and EMMPRIN with clinicopathologic parameters and prognosis of IHCCA. MMP-2 and EMMPRIN expression in 106 cases of IHCCA tissues and 15 cases of normal bile ducts were examined by immunohistochemical staining. Then, the association of MMP-2 and EMMPRIN expression with clinicopathologic parameters and patients’ prognosis was analyzed. The positive expression levels of MMP-2 and EMMPRIN associated significantly with various clinicopathologic risk factors, such as poor histologic differentiation (p = 0.03, 0.02), higher TNM stages (p = 0.02, 0.01) and decreased tumor-specific survival. In particular, the tumor-specific survival rate of the patients with MMP-2+/ EMMPRIN+expression was the lowest (p < 0.01). Using Cox regression analysis of the 89 patients, the conjoined expressions of MMP-2-/ EMMPRIN-, MMP-2+/ EMMPRIN +, histologic differentiation, and the clinical TNM stages of tumorous tissues were independent prognostic indicators of IHCCA (p < 0.01, p < 0.01, p = 0.02, p = 0.01 and p = 0.01, respectively). MMP-2 and EMMPRIN expression in primary tumor predicts an unfavorable prognosis in IHCCA, suggesting a crucial role of the two markers in progression of human IHCCA.     

Combined Expression of Metastasis Related Markers Naa10p,SNCG and PRL-3 and its Prognostic Value in Breast Cancer Patients

Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognosticvalue for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels ofN-α-acetyltransferase 10 protein (Naa10p), synuclein-γ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancerwere identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3- subgroup showed bestprognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p,SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overallsurvival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients withlymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, thecombined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classificationsystem, may provide a precise estimate of prognosis of breast cancer patients.     

Ubiquitin-specific Protease 14 Expression Associated with Intrahepatic Cholangiocarcinoma Cell Differentiation

The purpose of this study was to identify the gene alterations amplified from AO16 primer and examine whetherthe expression patterns of USP14 in clinical specimens from patients with intrahepatic cholangiocarcinoma (ICC)is associated with cancer cells. DNA from tumor and corresponding normal tissues of 52 patients was amplifiedwith 33 arbitrary primers. The DNA fragment that altered most frequently in ICC was cloned, sequenced, andidentified by comparison with known nucleotide sequences in the genome database. The DNA copy numbers ofthe allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted asallelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalanceand clinicopathological parameters of ICC patients were evaluated by χ2-tests. The Kaplan-Meier method wasused to analyze survival rates. Immunohistochemically, USP14 showed weak cytoplasmic staining in normalbile duct epithelial cells. It was strongly detected in 21 cancer patients (43.8%). There were correlations betweenUSP14 expression level and the clinicopathological features of ICC, histological grade (P < 0.05). However,there were no significant differences in age, gender, tumor size, metastasis, lymph node metastasis, and staging.USP14 expression was related to cholangiocarcinoma cell differentiation. Due to their emerging role in controlof multiple signaling pathways and oncoproteins, USP14 inhibitors may be useful for anticancer agents.     

胆管细胞型肝癌的CT诊断

目的探讨肝内胆管细胞癌的CT表现及其诊断价值。方法对47例经病理证实为胆管细胞型肝癌病人的CT表现进行分析。结果平扫均为低密度,35例可见更低密度区,18例可见病变区胆管扩张,12例胆管结石影,9例局部肝包膜回缩,13例肝叶萎缩,增强后早期的边缘增强、门脉期网格状增强及延迟期病灶向心性增强是最常见的征象。结论胆管细胞型肝癌CT表现具有一定特异性,有利于提高术前诊断率。     

Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer

The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n = 7) and nonmalignant (n = 7) cryoconserved breast tissue samples as well as in eight breast cancer cell lines by RT-PCR. Furthermore, protein expression of PRL-3 was analysed semiquantitatively by immunohistochemistry in ductal breast carcinoma in situ (n = 135) and invasive breast cancer (n = 147) by use of tissue microarray technology (TMA). In 24 lymph node-positive patients we selected the corresponding lymph node metastases for analysis of PRL-3 expression, and a validation set (n = 99) of invasive breast cancer samples was examined. Staining results were correlated with clinicopathological parameters and long-term follow-up. PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue. For PRL-1 and PRL-2 expression no significant differences were observed. Staining of TMAs showed PRL-3 expression in 85.9% ductal carcinoma in situ and 75.5% invasive breast carcinomas. Analysis of survival parameters revealed a shorter disease-free survival (DFS) in patients with PRL-3-positive carcinomas, and in particular a significantly shorter DFS in nodal-positive patients with PRL-3 overexpressing tumours as compared to PRL-3-negative breast carcinomas (66+/-7 months (95% CI, 52-80) vs 97+/-9 months (95% CI, 79-115); P = 0.032). Moreover, we found a more frequent expression of PRL-3 in lymph node metastases as compared to the primary tumours (91.7 vs 66.7%; P = 0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome.     

Increased Expression of the PRL-3 Gene in Human Oral Squamous Cell Carcinoma and Dysplasia Tissues

Phosphatase of regenerating liver (PRL) belongs to a class of the protein tyrosine phosphatase family, whichis known so far to consist of 3 members, PRL-1, PRL-2, and PRL-3. The aim of this study was to uncover therole of PRL genes in development of oral malignancy. We analyzed expression levels of the 3 PRL genes in 50human oral squamous cell carcinomas (OSCCs), 11 dysplasia and 12 normal mucosa tissues by a real-time RTPCRmethod. PRL-3 but not PRL-1 or PRL-2 expressions were significantly higher in OSCC and dysplasia thanin normal mucosa tissues. Additionally, PRL-3 expressions were significantly higher in OSCC tissues harboringdominant-negative p53 or recessive p53 mutation than in those harboring wild-type p53. These results suggestthat PRL-3 plays a role in oral cancer development and can be useful as a marker of pre-malignant and malignantlesion of oral mucosa.     

不同手术方法治疗肝内胆管癌的临床效果评价及预后危险因素分析

目的探讨不同手术方法治疗肝内胆管癌的临床效果及影响预后的危险因素分析。方法选取肝内胆管癌患者106例,所有患者行术前诊断评估,并根据不同的手术治疗方法分为手术根治切除治疗(根治组)、姑息性切除与辅助治疗(姑息治疗组)、对症治疗(经皮途径也能完成胆道引流)(对症治疗组),并对不同手术切缘的生存率及影响预后的因素进行分析。结果根治组患者的预后优于姑息治疗组,姑息治疗组患者的预后优于对症治疗组,生存率及中位生存时间由高到低为手术根治组>姑息治疗组>对症治疗组。单因素分析发现术前CA19-9、ALT以及淋巴结转移与预后相关(P<0.05),患者的性别、年龄、肝硬化、白蛋白以及合并结石与预后无关(P>0.05);行Cox回归分析发现,淋巴结转移、CA19-9、AJCC分期、肿瘤多发以及谷丙转氨酶为肝内胆管癌患者长期生存预后因素。手术方式及手术切缘对预后均有影响。结论肝内胆管癌患者术前完善各项相关检查,对疾病的准确诊断评估具参考价值,根治性手术治疗可明显改善患者预后。     

血管内皮生长因子在大肠癌中的表达及预后价值

目的：研究血管内皮生长因子（ＶＥＧＦ）在朋肠癌中的表达及其与临床病理特征的关系。方法：采用免疫组织化学方法检测８０例大肠癌手术标本肿瘤组织内的血管内皮生长因子（ＶＥＧＦ）和微血管计数（ＭＶＤ）。结果：ＶＥＧＦ表达阳性率为６１．２％,ＶＥＧＦＤ表达阳性的肿瘤组织其ＭＶＤ明显高于阴性者（Ｐ＜０．０５）。ＶＥＧＦ表达与肿瘤的浸润性生长、浆膜浸润、淋巴结转移和肝转移有明显相关性（Ｐ＜０．０５）。此外,ＶＥ     

肝内胆管癌治疗靶点的研究进展

肝内胆管癌(ICC)侵袭性强、预后差,目前缺乏有效的辅助治疗措施.随着对ICC相关肿瘤微环境、基因、蛋白、表观遗传修饰、信号通路等深入研究,潜在治疗靶点不断被发现.本文就近期发现的ICC潜在治疗靶点作一综述.     

PRL-3在乳腺癌组织及细胞系中的表达

目的:研究乳腺浸润性导管癌组织及乳腺癌细胞系中PRL-3的表达,同时在乳腺癌细胞系中应用SOV抑制剂在不同时间点检测PRL-3的表达情况。方法:应用western blotting方法检测乳腺浸润性导管癌及乳腺癌细胞系中PRL-3的表达,且在乳腺癌细胞系中加入不同浓度的SOV抑制剂后在不同时间点检测PRL-3的表达情况。结果:在乳腺浸润性导管癌组织中PRL-3的表达明显高于其癌旁乳腺组织,统计学显示P<0.01,且有淋巴结转移组的表达也显著高于无淋巴结转移组(P<0.01)。应用不同终浓度的SOV(0、2、5、10μmol/L)处理BT549细胞24h、48h、96h、120h后,结果显示PRL-3的表达水平随着SOV浓度的增高表达逐渐下降,呈现出明显的时间-剂量效应关系。结论:PRL-3可能将作为乳腺癌的一种诊断和治疗的靶点,而且其表达的增高会加速乳腺癌的转移。     

Clinicopathologic Significance of Sox2, CD44 and CD44v6 Expression in Intrahepatic Cholangiocarcinoma

Embryonic stem cells (ESC) and cancer stem cells (CSC) have a capacity for self-renewal and differentiation into multiple cell lineages. Sox2 plays a critical role in ESC and has been shown to participate in carcinogenesis and tumor progression in many human cancers. CD44 and CD44v6 are putative CSC markers and their association with tumor progression, metastasis, and tumor relapse after treatment has been demonstrated. We evaluated the immunoexpression of Sox2, CD44, and CD44v6 in 85 cases of Intrahepatic cholangiocarcinomas (IHCC) and assessed their prognostic significance. Sox2 expression showed a significant association with lymph node metastasis (p?=?0.025), T4 stage (p?=?0.046), and worse overall survival (p?=?0.047). Greater expression of Sox2 was observed in IHCC with poor differentiation, vascular invasion, and stage IV, without statistical significance (p?>?0.05). CD44 expression showed an association with periductal infiltrative type (p?=?0.034), poor differentiation (p?=?0.012), and vascular invasion (p?=?0.009). CD44v6 expression was evident in patients with stage IV (p?=?0.019). These results demonstrated that Sox2 expression is associated with aggressive behavior and poor overall survival in IHCC.     

Expression of Smad7 in Cholangiocarcinoma: Prognostic Significance and Implications for Tumor Metastasis

Background: There are few molecular markers known to predict cholangiocarcinoma (CCA) prognosis.Smad7 has a certain relationship with epithelial-mesenchymal transition (EMT), but its relevance to CCA inunclear. Therefore expression and clinical significance of Smad7 in CCA was the focus of this study. Methods:Expression of Smad7, E-cadherin and vimentin was assessed in 41 patients with CCA by immunohistochemistryand analyzed for associations with clinical parameters. Results: Smad7 and vimentin expression in the CCA tissuewas dramatically higher than that in adjacent tissues. In addition, Smad7, vimentin and E-cadherin expressionwas significantly associated with CCA lymph node metastasis and perineural invasion(P≤0.05), but not otherfactors, such as gender, age, tumor location, tumor type and tumor differentiation degree (P>0.05). The overallsurvival and relapse-free survival rate was significantly higher in patients with negative Smad7 expression thanthose with positive Smad7 expression. Conclusion: EMT phenomena may occur in the process of CCA invasionand metastasis. Smad7, which was highly expressed in CCA, may be considered to be one feedback regulatorin late stages and could have potential as a prognostic indicator for clinical assessment.     

肝细胞癌和肝内胆管细胞癌流行病学研究进展

摘 要：原发性肝癌在全球恶性肿瘤死因中位居第4位。肝细胞癌和肝内胆管细胞癌是其最常见的两种病理类型。虽两者均属原发性肝癌,但在病因学、流行病学、临床诊疗与预后等方面均有差别。该文就近年来肝细胞癌和肝内胆管细胞癌的流行病学研究进展作简要综述。     

PRL-3基因在结直肠癌原发灶中的表达及其临床意义

背景与目的：据报道，PRL-3基因表达在结直肠癌中具有显著的转移相关性。本研究探讨PRL-3基因在结直肠癌原发灶中的表达强度及其与主要临床病理学指标的相关性，以及在结直肠癌预后判断中的临床意义。方法：提取1998--2000年接受手术治疗并且具有完整随访信息的结直肠癌患者196例，采用免疫组织化学技术检测PRL-3表达情况，同时收集相关临床病理资料和随访信息进行相关性分析和预后研究。结果：在196例标本中，PRL-3高表达阳性率为49．5％（97／196），与肿瘤的组织分化程度、脉管侵犯、Dukes分期、手术性质以及术后转移的发生相关；单因素和多因素分析提示PRL-3表达是结直肠癌患者的重要预后因素。结论：PRL-3的表达是结直肠癌患者的一个新的预后指标，此基因的高水平表达提示术后脏器转移发生的可能性升高，并且和术后生存时间的缩短关系密切。