The targeted expression of interleukin-2 in human hepatocellular carcinoma cells

To improve the safety and efficiency of human hepatocellular carcinoma (HCC) gene therapy, we explored the use of a liver-specific promoter and a tumor-specific enhancer to achieve regular IL-2 gene expression for treatment of HCC. The human alpha-fetoprotein (AFP) enhancer [E(AFP)] and the albumin promoter [P(ALB)] were amplified from human genomic DNA. We used eukaryotic expression vector pcDNA-3 for the delivery of the IL-2 gene because this plasmid is a non-transient, fast-selection expression vector. A recombinant plasmid was constructed including the selectable marker neoR gene and the human IL-2 gene derived by the E(AFP) - P(ALB). The liver-predominant expression pattern of the IL-2 gene was observed in the medium of the transfected cells. When human HCC cell lines displaying different levels of AFP and non-hepatocyte tumor cell lines were transfected with the recombinant plasmid, IL-2 was expressed highly in AFP and albumin-positive HCC cells, but low in nonhepatocyte tumor cells. Moreover, the expression level of IL-2 gene was positively proportional to the level of AFP expression in the transfected cells.     

Production of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: histologic and immunohistochemical analyses of 35 cases

By immunoperoxidase histochemical staining of formalin-fixed paraffin-embedded sections, the production of alpha-fetoprotein(AFP), albumin(ALB), transferrin(TF), alpha-1-antitrypsin(AAT), and human chorionic gonadotropin(HCG) was examined in 35 operatively resected stomach cancers with elevated serum AFP levels (higher than 20 ng/ml as determined by radioimmunoassay). Cells positive for AFP were found in 19 cases (54%). In 29 cases (83%), some tumor cells contained normal serum proteins (ALB, TF, or AAT). All 19 tumors with AFP-positive cells also stained positively for two or three kinds of normal serum proteins. In some cases, AFP and normal serum proteins were localized in the same cells. There were two cases in which metastatic tumors produced AFP, whereas the primary sites did not. In nine cases (26%), HCG was present in tumor cells and HCG- and AFP-positive cells were coexistent in six tumors. Histologic examination of AFP-producing stomach tumors revealed medullary or papillotubular arrangements with marked nuclear atypia and eosinophilic granular or clear cytoplasms containing no glycogen or mucin. Some tumors with medullary patterns resembled liver cell carcinomas. Concordant phenotypic expression of AFP and normal serum protein production appears to be a general feature of AFP-producing tumors such as liver cell carcinoma, yolk sac tumor, and stomach cancer.     

Spindle cell tumors resected from male patients with germ cell tumors. A clinicopathologic study of 14 cases.

We identified 14 male germ cell tumor patients (13 of whom had received prior chemotherapy) in whom distinctive neoplasms composed of spindle to stellate cells set in a myxoid to collagenous stroma containing numerous blood vessels developed. These neoplasms were cytokeratin-positive and vimentin-positive and alpha-fetoprotein (AFP)-negative. Ten patients with neoplasms of low cellularity and no mitoses have not had tumor recurrences, whereas four patients with more cellular and mitotically active tumors have experienced either recurrences or death. We recommend simple surgical excision, without additional chemotherapy, for the hypocellular, mitotically inactive cases. The transition from mitotically active spindle cell tumors to frankly sarcomatous areas in three cases indicates that these lesions may be the substratum for the development of sarcomas in some patients with germ cell tumors. Based on their histologic appearance and immunohistochemical profile, as well as preceding evidence of yolk sac tumor (YST) in 11 patients (data incomplete in 3 cases), we speculate that many of these cases represent overgrowth of a spindle cell component of YST that is selected for by chemotherapy.     

Clinical significance of combination study of apoptotic factors and proliferating cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common recurrence diseases, which affects the patient's prognosis. The aim of this report is to evaluate recurrence risk after primary treatment by the combination study with the clinical features and immunohistological findings. METHODS: 153 removable HCCs were examined by immunohistochemical study of the proliferating cell nuclear antigen (PCNA), p53, or Bax. The relationships of these factors with histological grades, the presence of intra-hepatic metastasis (IM), tumor size, value of serum alpha-fetoprotein (AFP), and prognosis were studied. PCNA labeling index (LI) was calculated to count positive nuclei in 1,000 cells. RESULTS: PCNALI was significantly higher in cancer and correlated with tumor size. PCNALI and the tumor diameter in themselves could be a good predictor for patient prognosis and the combination study of them was an even stronger indicator. The value of AFP was significantly higher in positive p53 cases. The incidence of p53 was associated with histological types. The presence of IM was found in negative Bax cases of main tumors. The appearance of Bax was not correlated with histological types. The incidence of p53 or Bax was indicated to distinguish the patient prognosis of the lower grade histological cases, in which differences could not be found by the routine histological study. CONCLUSIONS: The combination study of the immunohistochemical findings and the clinical features could be one of the most important aids in interpreting the status of HCC.     

In vitro alpha-fetoprotein synthesis by monkey hepatocellular carcinoma.

Five monkeys were treated ip with N-nitrosodiethylamine (DENA), and one was treated with 1-nitrosopiperidine (PIP), starting within 2 months of birth, until hepatocellular carcinoma (HCC) developed. All animals except the PIP-treated monkey had much elevated serum alpha-fetoprotein (AFP) values. Fresh, minced, biopsy-derived tumor was cultured with L-[14C]leucine and L-[14C]lysine. Synthesis of AFP was determined by radioimmunoassay and by specifically precipitable [14C]AFP. Good agreement between these two parameters was obtained for the 4 DENA-induced tumors synthesizing AFP in culture. Tumor from 1 DENA-treated monkey did not synthesize AFP. In addition, neither normal liver nor tumor from the PIP-treated monkey showed AFP synthesis. Rates of synthesis were 0.37-5.50 ng AFP/mg tumor/day, or 0.0012-0.0183 pg AFP/cell/day (if one assumes 3.0 X 10(5) cells/mg tissue) over 48 or 72 hours. Different nodules from the same animal had similar rates of synthesis. For tumors that synthesized AFP in culture, a positive correlation was generally found between rate of synthesis and serum AFP level. The rate of in vitro AFP synthesis observed was lower than that of immunoglobulin synthesis in human myeloma or of AFP synthesis in a rat HCC, but it was close to the estimated rate of AFP synthesis in a monkey HCC line in long-term culture.     

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Biochemical and immunohistochemical analyses were done on five cases of gastric carcinoma with excessive production of alpha-fetoprotein (AFP). Histologic and ultrastructural examination of these cases showed conventional poorly differentiated adenocarcinoma of cuboidal or polygonal tumor cells in the medullary area with scattered AFP-positive cancer cells. Comparative studies on serum AFP between these cases and in hepatocellular carcinoma (HCC) or in testicular yolk sac tumor cases using concanavalin A (ConA)-affinity and lens culinalis agglutinin A (LCA)-affinity sepharose columns revealed that the AFP derived from four cases had a high ConA nonadsorping rate and high LCA-reactive fraction similar to that of yolk sac tumor. The AFP from one case had a small LCA-reactive fraction similar to that of HCC. Further immunohistochemical study using several markers for liver cells or germ cell tumor did not show additional evidence of these tumor cells to differentiate into liver cells or yolk sac tumor cells. Thus, this study indicates that AFP-producing gastric carcinomas are not always derived from hepatoid differentiation of the foregut. These gastric carcinomas might be categorized into medullary tumor with gastrointestinal tract-specific AFP.     

NET-1蛋白在肝癌中的表达和意义

目的研究NET-1基因在肝癌中的表达和意义,分析其与临床病理因素的相关性。方法Western blot法检测8例肝癌组织中NET-1的表达,免疫荧光细胞化学法检测肝癌SMMC-7721细胞中NET-1蛋白的表达,免疫组化法检测130例肝癌石蜡包埋组织中NET-1蛋白的表达。结果Western blot法检测显示,8例肝癌组织匀浆中均有NET-1的表达。免疫荧光细胞化学激光共聚焦观察显示,NET-1在SMMC-7721细胞浆中表达呈不规则颗粒状,分布在高尔基体附近。免疫组化结果显示,肝癌组织中NET-1蛋白检出率为96.9%(126/130),其表达强度与癌细胞学类型密切相关;在透明细胞型、多形细胞型和肉瘤样型中,NET-1蛋白检出率和阳性强度显著高于肝细胞型(P< 0.05)。NET-1基因与癌病理分级、临床分期和癌伴肝炎肝硬化呈等级正相关,而与癌伴片块状坏死呈负相关(P均<0.05),与患者AFP水平、肿瘤大小及肿瘤生长方式无明显相关。结论在肝癌中,NET-1表达于胞浆,定位于近高尔基体处。NET-1蛋白表达可能促进肝癌细胞失控性增生和失分化。     

Hepatocellular carcinoma and liver tumors in South African children: a case for increased prevalence

BACKGROUND: The high regional incidence of hepatocellular carcinoma (HCC) in South Africa also may be present in children of the region, although the link to hepatitis B (HBV) appears less clear. The objective of this study was to assess the incidence and probable causes of HCC in South African children. METHODS: Data were obtained from seven participating pediatric oncology units and from the tumor registry to review hepatic tumors in children in South Africa. RESULTS: One hundred ninety-four children (ages 0-14 years) presented with malignant primary hepatic tumors (1988-2003). One hundred twelve tumors (57%) were hepatoblastoma (HB), 68 tumors (35%) were hepatocellular carcinoma (HCC) (including 9 patients with the fibrolamellar variant, 6 of which occurred in black children), 10 tumors (5%) were sarcoma of the liver, and 4 tumors were lymphoma. The ratio of HB to HCC (1.67) was markedly lower compared with other reports, suggesting a greater prevalence of HCC. Correlation with population statistics indicated an incidence of 1.066 malignant liver tumors per year per 10(6) children age < 14 years (HB, 0.61 per 10(6) children; HCC, 0.39 per 10(6)). Two-thirds of patients with HCC were positive for HBV surface antigen (HBsAg), and HCC occurred mostly in black African patients (93%). The mean age of onset was 1.47 years for HB and 10.48 years for HCC. A preponderance of males (3.5:1.0) was noted in the HBsAg-positive group that was not reflected elsewhere. Serum alpha-fetoprotein (AFP) levels were raised both in patients with HB (100%; most AFP levels were very high) and in patients with HCC (69%), although 15% of patients with HCC had low or normal AFP levels. CONCLUSIONS: It appeared from the current results that HCC is more prevalent among children in South Africa compared with the children in more developed countries, although their rates were lower that the rates noted in adults. A collaborative approach will be required to improve their diagnosis and management.     

Hepasphere载药微球栓塞治疗中晚期肝细胞肝癌的安全性及疗效分析

目的:采用Hepasphere载药微球栓塞（DEB-TACE）治疗中晚期肝细胞癌（HCC）,观察该疗法的安全性及疗效。方法:评估接受DEB-TACE治疗HCC患者术前术后肝功能,血清AFP水平变化以及术后不良反应、短期疗效和生存期。结果:从2014年7月到2017年10月纳入研究HCC患者24人（男21人,女3人）,中位年龄为57（24～82）岁,肿瘤平均最长径为（9.3±4.0）cm。根据BCLC分期,包括B期5人,C期19人。合计接受DEB-TACE治疗31人次,成功率100%。DEB-TACE术前、后ALB、ALT、AST、T.BIL和AFP无统计学意义（P>0.5）。DEB-TACE术后30天内未见肝梗死等严重并发症,不良反应包括发热6例（19.4%）、恶心1例（3.2%）,肝区疼痛4例（12.9%）。随访时间范围从3.9～40.0个月,平均随访13.2个月。根据改良RECST标准,治疗后1、3、6个月获得的疾病缓解率为58.3%、45.8%和40.9%,疾病控制率为91.7%、83.3%和86.4%。1、2年的存活率为87.5%和58.3%。截止到研究终点,中位生存期为25.6个月。结论:DEB-TACE对治疗中晚期HCC安全好,短期疗效稳定。     

Localization of small liver tumors.

Thirty-six patients with small liver tumor were diagnosed by alpha-fetoprotein (AFP); sonography, and computed tomography (CT), and underwent hepatectomy. The pathological types included 23 hepatocelluler carcinoma (HCC), 11 hepatic cavernous hemangioma, and 2 secondary liver cancer. In 22 patients, the tumor nodules were located in the right lobe and 14 cases in the left lobe. The diagnostic accuracy rate of CT was 100% for HCC and secondary liver cancer, but for hepatic cavernous hemangioma it was only 72.2%. However, the accuracy rate of sonography was as high as 81.8% for hepatic cavernous hemangioma and only 60.4% for liver malignancies. The positive rate of AFP for the HCC patients of this series was only 66.6%. The method of intraoperative detection of small liver tumor is introduced, if the tumor was invisible grossly or nonpalpable during exploratory laparotomy. In the series, 7 cases in whom the right lobe lesion was too small to be located by routine manual examination during exploratory laparotomy were detected by this method, and all small liver tumors were resected successfully.     

Identification of alpha-fetoprotein-derived peptides recognized by cytotoxic T lymphocytes in HLA-A24+ patients with hepatocellular carcinoma

Alpha-fetoprotein (AFP) has been proposed as a potential target forT-cell-based immunotherapy for hepatocellular carcinoma (HCC), but the number of its epitopes that have been identified is limited and the status of AFP-specific immunological responses in HCC patients has not been well-characterized. To address the issue, we examined the possibility of inducing AFP-specific cytotoxic T cells (CTLs) using novel HLA-A*2402-restricted T-cell epitopes (HLA, human leukocyte antigen) derived from AFP and then analyzed the relationship between its frequency of occurrence and clinical features associated with patients having HCC. Five AFP-derived peptides containing HLA-A*2402 binding motifs and showing high binding affinity to HLA-A*2402 induced CTLs to produce IFN-gamma and kill an AFP-producing hepatoma cell line. The frequency of AFP-specific CTLs was 30-190 per 1 x 10(6) peripheral blood mononuclear cells, which was the same as that of other immunogenic cancer associated antigen-derived epitopes. Analyses of the relationships between AFP-specific CTL responses and clinical features of patients with HCC revealed that AFP epitopes were more frequently recognized by CTLs in patients with advanced HCC correlating to tumor factors or the stage of TNM classification. The analyses of CTL responses before and after HCC treatments showed that the treatments changed the frequency of AFP-specific CTLs. In conclusion, we identified five HLA-A*2402-restricted T-cell epitopes derived from AFP. The newly identified AFP epitopes could be a valuable component of HCC immunotherapy and for analyzing host immune responses to HCC.     

RECK及MMP-14在肝细胞肝癌组织中的表达及其临床意义

目的：探讨RECK及MMP-14与肝细胞肝癌（HCC）的侵袭转移以及预后的关系。方法：用逆转录聚合酶链反应（RT-PCR）技术检测61例HCC患者癌组织、癌旁肝组织以及18例正常肝组织中RECK及MMP-14的mR-NA表达情况;并分析RECK及MMP-14的mRNA的表达与相关临床参数的关系。结果：RECKmRNA在HCC组织中的表达水平显著低于在癌旁肝组织和正常肝组织中的表达水平（P〈0.01）,而在癌旁肝组织和正常肝组织中的表达水平差异无显著性（P〉0.05）;MMP-14mRNA在肝癌组织的表达水平显著高于在癌旁肝组织中的表达水平（P〈0.01）,在癌旁肝组织中的表达水平显著高于在正常肝组织中的表达水平（P〈0.01）。RECKmRNA和MMP-14mRNA在HCC组织中的表达呈负相关（P=0.027）,而两者在癌旁肝组织及正常肝组织中的表达无相关性。RECKmRNA在HCC组织中的表达水平与临床分期、门静脉癌栓、肝外转移及术后复发等明显相关,而与肿瘤直径、肿瘤个数、血清AFP水平、肿瘤分化程度以及癌旁有无肝硬化等无明显关系。MMP-14mRNA在HCC组织中的表达水平与临床分期、门静脉癌栓、肝外转移、术后复发、肿瘤直径大小明显相关,而与肿瘤数目、血清AFP水平、肿瘤分化程度以及癌旁有无肝硬化等无明显关系。结论：本研究提示RECK及MMP-14的mRNA表达与HCC的浸润转移有关,RECK及MMP-14可能在肝细胞肝癌的发生、发展中起重要作用,有可能作为预测肝癌复发、转移的参考指标。     

Evaluation of Osteopontin as a Biomarker in Hepatocellular Carcinomas in Egyptian Patients with Chronic HCV Cirrhosis

Background: Hepatocellular carcinoma (HCC) is a high incidence disease in Egypt with a poor prognosis andsurvival. Biomarkers are important for diagnosis of HCC at an early stage. Osteopontin (OPN), a glycoprotein secreted bymacrophages, osteoblasts, and T cells, is also highly expressed in a variety of tumors, such as examples in the breast, colon,and stomach. The present study aimed to correlate the serum level of OPN in HCV-positive hepatocellular carcinomapatients, with OPN expression in tumor and non-tumor liver tissues in order to identify its efficacy as a biomarkerfor diagnosis. Material and Methods: Out of total of 146 patients, 80 were selected for inclusion in the study. Bloodsamples as well as specimens of tumor and non-tumor liver tissue were collected. In addition, blood samples from 20healthy volunteers were obtained as controls. Serum OPN and alpha-fetoprotein (AFP) were evaluated by ELISA forHCC and control groups. OPN and AFP gene expression were examined by real-time PCR, after homogenization andDNA extraction from serum samples and liver tissues. Results: It was found that serum OPN levels were significantlyhigher in the HCC group compared to normal group (P=0.009), with a strong positive correlation with AFP expression.However, there was no significant difference between OPN expression in tumor and non-tumor liver tissue. Conclusion:Serum OPN is highly suggested to be a professional candidate for HCC early diagnosis, with a diagnostic ability andaccuracy equal or higher than for AFP.     

经肝动脉化疗栓塞联合射频消融治疗原发性肝细胞癌合并门静脉癌栓的预后影响因素分析

背景与目的：经肝动脉化疗栓塞（transcatheter arterial chemoembolization,TACE)是否为治疗原发性肝细胞癌（hepatocellular carcinoma,HCC）合并门静脉癌栓（portal vein tumor thrombus,PVTT）的绝对禁忌,目前尚无定论。该研究旨在探讨TACE联合射频消融（radiofrequency ablation,RFA）治疗HCC合并PVTT的预后影响因素。方法：回顾性分析2011年1月1日—2013年12月31日于郑州大学附属肿瘤医院行TACE联合RFA治疗的HCC合并PVTT的157例患者的临床资料及随访数据,单因素及多因素Cox回归分析人口学资料、实验室指标及临床资料与生存时间和肿瘤转移复发情况的关系。结果：多因素Cox回归结果显示,在调整和控制其他因素后,血清白蛋白（albumin,ALB）水平为TACE联合RFA治疗后HCC合并PVTT患者3年生存及降低肿瘤复发转移风险的保护性因素,术前甲胎蛋白（alpha-fetoprotein,AFP）、丙氨酸转氨酶（alanine aminotransferase,ALT）、天门冬氨酸转氨酶（aspartate transaminase,AST）水平、门静脉癌栓部位及肝功能Child Pugh分级为患者3年生存的独立危险因素;AFP、AST水平及门静脉癌栓部位为肿瘤复发转移的独立危险因素。结论：TACE联合RFA并非治疗HCC合并PVTT的绝对禁忌,在治疗前对患者进行相关因素评估有助于更好地选择治疗方法和时机,从而提高HCC治疗水平。     

Hepatocellular Carcinoma and its Early Detection by AFP Testing in Mongolia

Liver cancer is one of the leading causes of cancer death in Mongolia. Since 1982-1986 , when HCC became themost frequent cancer among the Mongolian population, the rate has been increasing continuously. In the period2000-2005 years 35.3%of all newly registered cancer cases were liver cancers, with an incidence rate of 51.3 per100,000 population. Compared to the previous 5 year period, the rate increased by 11%. The objective here was toanalyze hepatitis B (HBV) and C virus (HCV)-related HCC cases and to evaluate the possibility of tumor marker(AFP) testing for early detection in Mongolia. Sera from a total of 513 patients with chronic liver diseases, livercirrhosis and HCC were analyzed for liver function (ALAT, ASAT) and hepatitis virus markers (HBsAg, anti-HCV).Sera from 316 patients were also examined for alpha-fetoprotein (AFP) levels. The overall incidence of HBsAg oranti-HCV were very high ( 95.3%) among all patients. Some 33.5% (66/197) of patients with HCC were positive forHBsAg and 45.2% (89/197) for anti-HCV. Moreover, 17.3% ( 34/197) of HCC patients demonstrated co-infectionwith HBV and HCV. AFP levels were elevated in 4.6% (11/238) and 29.5% (23/78) of chronic hepatitis and cirrhosispatients, respectively. In HCC cases, 84.3% (166) of patients had increased level of AFP ranging from 32ng/ml tomore than 400 ng/ml. We conclude that HBV/HCV infection is the main factor related to development of HCC inMongolia and that testing for AFP serum levels is a useful tool for early detection and diagnosis.     

肝组织和外周血中AFPmRNA定量分析及临床应用的研究

目的 :通过检测AFPmRNA在肝细胞癌 (hepatocellularcarcinoma ,HCC)患者肝组织和外周血中的基因表达 ,探讨AFPmRNA相对定量值作为HCC微转移指标的可能性 ,建立HCCAFPmRNA相对定量分析法。方法 :建立敏感的巢式逆转录聚合酶链反应体系 (Nested RT PCR) ,对肝组织和外周血中的AFPmRNA进行相对定量值分析。结果 :在 49例HCC及其癌旁和远癌组织、12例非肝肿瘤组织和 8例正常肝组织中AFPmRNA相对定量值阳性分别为 3 5例 ( 71 4% )、2 0例 ( 4 0 8% )、3例 ( 6 1% )、0例、0例 ;3 5例肝癌患者中有2 3例术前外周血AFPmRNA相对定量值为阳性 ( 65 7% ) ,明显高于肝硬化、急性肝炎、慢性肝炎患者和正常人外周血 ;HCC患者外周血术后 72hAFPmRNA相对定量值的阳性率 2 2 9% ( 8/3 5 ) ,与术前比较差异有统计学意义 ,P <0 0 1。结论 :肝组织和外周血中AFPmRNA相对定量分析可提高HCC阳性诊断率 ,并可作为HCC微转移的早期检测指标。治疗前后的变化对指导临床治疗及评价HCC治疗效果有重要参考价值     

小肝肿瘤的诊断和术中定位

本文复习经B型超声、CT及AFP诊为小肝肿瘤36侧,内肝细胞癌23例,海绵状血管瘤11例,转移癌2例。肿瘤最大径<3cm者14例,3—5cm22例,位于右肝叶22例,左肝叶14例。 CT对肝细胞癌和肝转移癌的诊断准确率为100％,对肝海绵状血管瘤的准确率为72.7％;B型超声为81.8％。AFP在23例肝细胞癌的阳性率为66.6％。 本文介绍了在术中不能看见或不能触到的小肝肿瘤的寻找方法,7例由此发现而顺利作了切除术,计肝细胞癌4例,海绵状血管瘤2例,转移癌1例。     

High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations

alpha-Fetoprotein (AFP) is often elevated in hepatocellular carcinoma (HCC). This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy. We showed that high AFP (> 200 ng/ml), which was associated with AFP mRNA expression in HCC (p = 0.00001), correlated with major clinicopathologic factors. Younger age (< or = 55 years; p=0.00001), hepatitis B surface antigen (HBsAg) in serum (p=0.00001), p53 mutation (p=0.008), large tumor (p=0.00001), vascular invasion (p=0.00001) and early tumor recurrence (p=0.00001) were significant associates of high AFP, while anti-HCV in serum and beta-catenin mutation in HCC had less frequent high AFP (p=0.013 and < 0.0001, respectively). We also showed that HCC with high AFP had a lower 10-year survival (p < 0.0001), particularly in large HCC (p < 0.0001). At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p=0.05), p53 mutation (p=0.0004), liver cirrhosis (p=0.0094), large tumor (p=0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors. In Cox proportional hazards regression analysis, high AFP remained a borderline significance (OR=1.2; CI=1.0-1.4) after adjustment for the effect of tumor size and tumor stage (p=0.0821). Furthermore, the detection of AFP mRNA in the liver of AFP mRNA-positive HCC was associated with more frequent early recurrence (p=0.0026) and might be a useful marker of intrahepatic spread. We therefore conclude that AFP elevation, more than a coincidental epiphenomenon, appears to contribute to vascular invasion and HCC progression and help to identify subsets of HCC patients with increased risk for early recurrence and poor prognosis after hepatectomy.     

Tissue antigen distribution in hepatocellular carcinoma

An immunohistochemical study on 63 hepatocellular carcinomas (HCC) was performed for the demonstration of alpha 1-antitrypsin (AAT), alpha-fetoprotein (AFP) and hepatitis B virus (HBV) antigens. AAT and AFP were also investigated in 54 cases of cirrhosis not associated with HCC. AAT was frequently expressed both in HCC (82.5%) and in cirrhosis (53.7%), whereas AFP was present in 41.2% of HCC and never detected in cirrhosis used as controls. These findings suggest that AFP is the more specific antigen for use as a marker of malignant cellular transformation. The HBsAg-positivity in 31.7% of HCC supports the hypothesis of a close link between virus B infection and the tumor.