Circulating Tumor Cells in Breast Cancer: A Step Toward Precision Medicine for Real-Time Monitoring of Metastasis

Background/Aims: Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive score based on degradation of glycosaminoglycans in the extracellular matrix for assessment of metastasis in patients with breast cancer. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of Metastases in patients with breast cancer. Material & Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19) and CA15.3 were assayed in metastatic breast cancer patients (88), non-metastatic breast cancer patients (129) and healthy control (32). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CTC-MBS = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1. CTC-MBS score produces AUC of 1 for differentiate patients with metastatic breast cancer from those with non-metastatic breast cancer with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered metastatic, whereas above 0 it is considered non-metastatic. Conclusion: CTC-MBS score is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer and could replace CA15.3 during screening and follow-up of breast cancer patients.     

Development of a novel score for early detection of hepatocellular carcinoma among high-risk hepatitis C virus patients

Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between vascular endothelial growth factor (VEGF) and HCC progression, we aimed to develop a novel score based on combination of VEGF and routine laboratory tests for early prediction of HCC. VEGF was assayed for HCC group (123), liver cirrhosis group (210), and control group (50) by enzyme-linked immunosorbent assay (ELISA). Data from all groups were retrospectively analyzed including α-fetoprotein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under receiving operating curve (ROC) were used to develop the score. A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-VEGF score)?=?1.26 (numerical constant?+?0.05?×?AFP (U l^?1)?+?0.038?×?VEGF (ng ml^?1)?+?0.004?×?INR???1.02?×?albumin (g l^?1)???0.002?×?platelet count?×?10⁹ l???¹ was developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91 % and specificity of 82 % at cutoff 4.4 (i.e., less than 4.4 considered cirrhosis and greater than 4.4 considered HCC). Hepatocellular carcinoma-VEGF score could replace AFP in HCC screening and follow up of cirrhotic patients.     

Presence of EpCAM‐positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma

Current imaging technologies do not sufficiently detect micrometastasis and therefore do not allow adequate stratification of patients with hepatocellular carcinoma (HCC) for curative or systemic therapy. In HCC, presence of stem cell‐like, epithelial cell adhesion molecule (EpCAM)‐positive cells correlates with tumor aggressiveness and formation of metastasis. Therefore, we investigated the prognostic relevance of EpCAM‐positive circulating tumor cells (CTCs) in patients with HCC. Blood from 78 patients (19 patients in the control cohort and 59 patients with HCC) was tested for CTCs with the CellSearch? system. Correlation analysis to overall survival (OS), the Barcelona Clinic Liver Cancer (BCLC) staging system, macroscopic and microscopic vascular invasion and alpha‐fetoprotein (AFP) levels were performed. We detected ≥1 CTC in 18/59 HCC patients and in 1/19 patients with cirrhosis or benign hepatic tumor (p = 0.026). OS was significantly shorter (460 vs. 746 days) in the CTC‐positive cohort (p = 0.017). Comparing BCLC stages, significant differences in CTC detection rates were also observed: BCLC stages A 1/9, B 6/31 and C 11/19 (p = 0.006). Ten of 18 patients with macroscopic and 10/16 patients with microscopic vascular invasion exhibited positive findings in CTC testing (p = 0.004 and p = 0.006). Furthermore, CTC results correlated to AFP (cutoff > 400 ng/mL) levels (p = 0.050). Our study demonstrates frequent presence of EpCAM‐positive CTC in patients with intermediate or advanced HCC and its prognostic value for OS with possible implications for future treatment stratification.     

CD147和CK19在肝细胞癌中的表达及临床意义

目的 探讨细胞外基质蛋白诱导因子（CD147）和细胞角蛋白19（CK19）在肝细胞癌（HCC）中的表达及临床意义。方法 采用组织芯片技术和免疫组织化学法检测CD147和CK19在272例HCC组织和81例癌旁组织中的表达情况。结果 CD147在HCC中的阳性表达率为73.53％（200／272）,在癌旁组织中的阳性表达率为13.58％（11／81）,差异有统计学意义（P＜0.05）。CK19在HCC组织中的阳性表达率为14.34％（39／272）,CK19在癌旁组织中无表达。在HCC中,CD147的表达与组织学分级、临床分期、术后无瘤生存时间、肿瘤直径、脉管或门静脉癌栓相关,与性别、年龄、肝硬化、AFP水平、HBV感染、淋巴结转移、病灶数目、肝被膜浸润及卫星灶无关（P＞0.05）;CK19在HCC中的表达与术后无瘤生存时间、组织学分级、肿瘤直径、肝硬化、卫星灶、淋巴结转移及临床分期有关,与性别、年龄、病灶数目、肝被膜浸润、AFP水平、HBV感染及脉管或门静脉癌栓无关（P＞0.05）。在HCC中,CD147 阳性表达者与阴性表达者的中位复发时间分别为13个月和48个月（P＜0.05）,中位生存时间分别为24个月和60个月（P＜0.05）;CK19阳性表达者与阴性表达者的中位复发时间分别为7个月和31个月（P＜0.05）,中位生存时间分别为13个月和42个月（P＜0.05）。 CD147的表达和CK19的表达无明显相关性（r=0.061,P=0.317）。结论 HCC中CD147和CK19的表达与预后密切相关,且两者均可作为HCC预后不良的判断指标。     

Cytokeratin-18 in Diagnosis of HCC in Patients with Liver Cirrhosis

Background: Hepatocellular carcinoma (HCC) is a common malignancy that occurs secondary to viral hepatitis B and C cirrhosis under the influence of environmental factors. In early stages, clinical diagnosis is often difficult and distinguishing HCC from cirrhosis and other hepatic masses by conventional tests is frequently not feasible. Physicians usually depend on measuring serum alpha-fetoprotein (AFP), but this marker has low sensitivity and specificity. The aim of this research was to determine any role of serum cytokeratin-18(Ck-18) as a marker for diagnosis of HCC in patients with liver cirrhosis. Patients and methods: We used ELISA to measure the serum levels of AFP and CK 18 in 60 Egyptian patients (30 cirrhotic and 30 with HCC) and 30 controls. Results: The Ck-18 level was significantly elevated in the HCC group (1247.8± 105.3U/L) when compared to the liver cirrhosis (834.1± 38.8 U/L) and control groups (265.2±83.1U/L). Ck-18 as a marker showed 95.6% sensitivity, 93.3% specificity and 98.8% accuracy. The mean serum AFP was 4901.4±2185.8ng/ml in the HCC group, 100.7±71.7 ng/ml in the cirrhotic group, and 4.0±1.2ng/ ml in controls. AFP showed 55. 7% sensitivity, 97. 7% specificity and 84.4% accuracy. Combined use of both Ck-18 and AFP improved the sensitivity to 98%. Conclusion: Serum cytokeratin-18 level can be used as a diagnostic biomarker for HCC with a higher sensitivity than AFP.     

肝细胞癌病理学微侵袭的影响因素对放疗靶区确定的潜在价值

目的 通过病理切片观察肝细胞癌镜下外侵特点,提供准确的病灶浸润范围,以指导临床医生确定放疗靶区范围.方法 搜集4年间149例肝细胞癌手术切除的病理标本及其相关临床资料,包括肿瘤最大直径、包膜情况、边界情况、门脉癌栓、TNM临床分期、Edmondson-Steiner分级、血清中AFP值、未梢血血小板计数、肝硬化程度.肿瘤切缘必须>1cm,术前影像学检查及术中探查均未发现原发肿瘤周边子灶.通过常规病理切片在显微镜下确定肝癌微侵袭灶距离.结果 肿瘤微侵袭灶距原发灶距离最远为4mm,范嗣O.5～4.0 mm,平均(1.64±0.09)mm.有微侵袭灶者较无侵袭灶者易出现复发,其复发率分别为44%(35/79)和29%(20/70)(P=0.047).肿瘤最大直径、包膜情况、边界情况、门脉癌栓、TNM临床分期、Edmondson-Steiner分级、血清中AFP值、末梢血血小板计数、肝硬化程度与微侵袭灶有关(P值均<0.05).通过对肿瘤最大直径、肿瘤包膜、门脉癌栓、血清中AFP值、末梢血血小板计数5项简单临床指标评分,O～2分者自包膜外扩2mm即能达到97%的准确性,>2分者准确性仅83%.结论 肝细胞癌的微侵袭灶外侵距离与肿瘤最大直径、肿瘤包膜、门脉癌栓、血清中AFP值、末梢血血小板计数有关,通过5项简单临床指标评分可初步判断外侵范围.     

Serum CA 19-9 and alpha-fetoprotein levels in primary hepatocellular carcinoma and liver cirrhosis.

Serum CA 19-9 and alpha-fetoprotein (AFP) levels were determined in 211 patients with liver cirrhosis and 27 with primary hepatocellular carcinoma (HCC) associated with liver cirrhosis. This was done to determine the usefulness of CA 19-9 level with respect to AFP level in distinguishing between these two illnesses, and to assess the influence of some clinical and biochemical variables on these tests in patients with liver cirrhosis with or without primary HCC. Pathologic AFP values were found in 23 of 27 (sensitivity, 85%) patients with HCC; CA 19-9 levels increased in only 12 of 27 (sensitivity, 44%) HCC patients, the values being comparable with those of patients with liver cirrhosis. In liver cirrhosis a substantial number of false-positive values was found for both markers, although they were higher for CA 19-9 (50 of 211 versus 39 of 211). In liver cirrhosis correlations were found between AFP level and alanine amino-transferase level; and between CA 19-9 level and (1) total bilirubin value, (2) alkaline phosphatase level, and (3) pseudocholinesterase level. The authors conclude that CA 19-9 level is a poor biochemical marker, inferior to AFP level, in the detection of a carcinomatous transformation of liver cirrhosis. The finding of false-positive AFP values in liver cirrhosis seems mainly attributable to cellular proliferation and necrosis. Cholestasis seems to greatly affect serum CA 19-9 level variations, probably by reducing its liver metabolism.     

肝癌免疫组化诊断谱的研究和应用

目的：探讨鉴别肝细胞癌（HCC）、肝内胆管癌（ICC）和肝转移性腺癌（MAC）的免疫组化诊断谱特点。方法：对手术切除的300例HCC、35例ICC和30例MAC分别进行AFP、Hep Pau 1、CK18、CK19、CA19－9、CD34和pCEA等7种免疫组化染色,将特异性和敏感性的综合性能计分（CCS）≥8分的抗体定为具有高度诊断价值。结果：CCS≥8分的抗体在HCC中为Hep Par 1和CD34,在ICC中为CK19,在MAC中无。Hep Par 1的CCS（9分）明显高于AFP（7分）,其对HCC的敏感性达到83.7%,特异性达到96．7％。结论：HCC的一线抗体由Hep Par 1和CD34组成,二线抗体由pCEA和AFP组成：ICC的一线抗体为CK19,二线抗体为CA19－9。由3种一线抗体组合成肝癌的核心免疫组化谱,酌情使用二线抗体,可以较好地解决对HCC、ICC和MAC之间的免疫病理诊断和鉴别诊断。     

Do CA 19-9 and TPA play a minor role as compared to AFP in diagnosing primary hepatocellular carcinoma?

This study was undertaken in order to compare the ability of 4 tumour markers to discriminate between liver cirrhosis patients with or without hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA 19-9 and tissue polypeptide antigen (TPA) were determined in 63 patients with liver cirrhosis and in 25 patients with HCC in liver cirrhosis. All 4 serum markers were found to be increased in a number of liver cirrhosis patients, regardless of the presence of HCC. AFP was found to be more elevated in HCC patients as compared to the other group; no difference was observed for CA 19-9, CEA and TPA. A significant correlation was detected in HCC patients between AFP and TPA. Significant correlation were detected in all except HCC patients between liver function tests and TPA. We can conclude that AFP determination remains as yet the only suitable marker able to detect HCC in liver cirrhosis. The newly introduced serum marker CA 19-9 is, as previously reported, unhelpful for CEA. TPA can in some instances (i.e. in the absence of an important hepatic cell necrosis or cholestasis) provide a clue to neoplastic growth.     

Caspase-Cleaved Cytokeratin 18 Fragment M30 as a Potential Biomarker of Macrovascular Invasion in Hepatocellular Carcinoma

Background and Aim

Extremely poor prognosis in hepatocellular carcinoma (HCC) patients with progressing disease was denoted by vascular invasion. Cytokeratin 18 (CK18) has been shown to be overexpressed in hepatocellular carcinoma so it is a valuable tumor marker; however, its role in vascular invasion is still unclear. This study aimed to predict CK18 as a predictive marker for macrovascular malignant invasion.

Methods

The present study was conducted on three groups of patients: group I included 91 HCC patients without macrovascular invasion, group II included 34 HCC patients with radiological evidence of vascular invasion, and group III included 110 control individuals subdivided into IIIA as healthy blood donors and IIIB as post-HCV cirrhotic patients without HCC.

Results

ROC curve of M30 fragments of CK18 was constructed for discrimination between HCC with and without macrovascular invasion. Optimum cutoff value was 304.5 ng/mL (AUC = 0.997, P < 0.001), sensitivity (100%) and specificity (98.8%). Regression analysis was conducted for prediction of macrovascular invasion within HCC patients. The following variables: higher levels of AST, M30, bilirubin, and AFP, lower levels of serum albumin, larger tumor size, child B score, and multiple lesions were associated with vascular invasion in univariate analysis. While in multivariate analysis, higher levels of AST and bilirubin and elevated levels of M30 and AFP serum were considered independent predictors for macrovascular invasion in HCC patients.

Conclusion

The present study suggests that increased M30 fragments of CK18 levels may be useful as a possible marker of early tumor invasiveness.

     

肝细胞癌患者外周血中Midkine、CTCs的表达水平及临床意义

目的:观察中期因子（Midkine）、循环肿瘤细胞（CTCs）在肝细胞癌患者外周血中的表达水平,并研究它们与肝癌临床病理参数之间的关系。方法:收集我院96例原发性肝癌患者临床资料为肝癌组,40例健康体检组作为对照组。采用酶联免疫吸附法（ELISA）和电化学发光法检测Midkine水平,采用阴性富集法检测CTCs计数。分析Midkine、CTCs在肝细胞癌患者外周血中的表达与临床病理参数之间的关系以及肝细胞癌患者外周血Midkine表达与CTCs表达的相关性。结果:肝癌组外周血Midkine的表达水平显著高于对照组（P＜0.001）;肝癌组外周血中CTCs阳性检出率(70.8%,68/96)显著高于对照组(7.5%,3/40)（P＜0.001）。肝癌患者外周血Midkine表达在肿瘤大小、血管侵犯、Child-pugh分级、AFP水平、BCLC分期及Edmondson-Steiner分级均有显著差异（P＜0.05）。肝癌患者外周血CTCs表达在血管侵犯、Child-pugh分级、AFP水平、BCLC分期及Edmondson-Steiner分级均有显著差异（P＜0.05）。本研究结果显示,96例肝癌患者中,上皮型CTCs阳性率为31.3%,间质型CTCs阳性率为44.8%,混合型CTCs阳性率为67.7%。三种CTCs类型在肿瘤大小、血管侵犯、AFP水平、BCLC分期及Edmondson-Steiner分级均有显著差异（P＜0.05）。Spearman相关性分析得出,外周血Midkine表达与CTCs表达呈正相关（r=0.531,P=0.007）。结论:肝细胞癌患者外周血Midkine与CTCs的表达均高于正常组,Midkine与CTCs可能在肝癌的发生发展中发挥作用,且两者在肝细胞癌患者外周血中的表达呈正相关。     

Enhanced detection of hepatocellular carcinoma.

BACKGROUND: Tumor markers in the early detection of tumors are promising tools that could improve the control and treatment of tumors. While alpha-fetoprotein (AFP) is a commonly used tumor marker in the detection of hepatocellular carcinoma (HCC), its sensitivity and specificity are insufficient to detect HCC in all patient samples. METHODS: We compared AFP with serum levels of vascular endothelial growth factors (VEGF and VEGF-A), insulin-like growth factor-2 (IGF-II), and the activity of the lysosomal enzyme alpha-L-fucosidase (AFU) in the sensitivity of detection of HCC and cirrhosis in Egyptian patients. RESULTS: The sensitivity of tumor detection using AFP was 68.2%. This level of detection was increased to 88.6% when AFP was evaluated in conjunction with AFU. The combined use of AFP and VEGF increased the sensitivity of detection to 95.5% in patients with HCC. The combination of the three markers yielded 100% detection sensitivity. VEGF-A showed a low specificity (20%), and IGF-II showed extremely low sensitivity (4.5%). CONCLUSIONS: We suggest that AFU or VEGF or both be measured with AFP to improve the detection sensitivity of HCC.     

CD147和CK19在肝细胞肝癌中的表达及临床意义

Objective

The aim of this study was to investigate the expressions of CD147 and CK19 in hepatocellular carcinoma (HCC) and their clinical significance.

Methods

The expressions of CD147 and CK19 were determined by tissue microarray and immunohistochemistry (IHC) in 272 cases of HCC and 81 cases of adjacent tumorous tissue.

Results

The positive expression of CD147 in HCC and adjacent tumorous tissue was 73.53% (200/272) and 13.58% (11/81) with significant difference (P < 0.05). The positive expression of CK19 in HCC and adjacent tumorous tissue was 14.34% (39/272) and 0 (0/81) with significant difference (P < 0.05). The positive expression of CD147 were closely correlated to the histological grade, clinical stage, tumor-free survival, diameter of tumor and embolus of cancer in aqueduct or portal vein; but not to the patients’ sex, age, liver cirrhosis, AFP level, infection of HBV, lymph node metastasis, number of tumor, invasion liver involucrum and the micro-satellites (P > 0.05). The expression of CK19 in HCC were closely correlate to the tumor-free survival, histological grade, diameter of tumor, liver cirrhosis, micro-satellites, lymph node metastasis and clinical stage; but not to patients’ sex, age, number of tumor, invasion liver involucrum, AFP level, infection of HBV and embolus of cancer in aqueduct or portal vein (P > 0.05). Among the patients of positive expression of CD147, the median replacing time and overall survival were 13 and 24 months, lower than 48 and 60 months in the patients of negative expression (P < 0.05). Among the patients of positive expression of CK19, the median replacing time and overall survival were 7 and 13 months, lower than 31 and 42 months in the patients of negative expression (P < 0.05). The expression of CD147 had no correlation with the expression of CK19 (r = 0.061, P = 0.317).

Conclusion

The positive of CD147 and CK19 closely correlate with the clinical prognosis of HCC, it may indicate poor prognosis of HCC.     

Tumor markers--personal experience. The use of tumor markers for cancer of digestive organs]

This review is concerned mainly with our experience in the use of tumor markers for cancer of digestive organs from study of tumor markers by the author over the past 20 years. Development of a radioimmunoassay for highly sensitive detection of alpha-fetoprotein (AFP) by Ishii et al. in 1971 enhanced the usefulness of screening for early hepatocellular carcinoma (HCC) occurring in the course of liver cirrhosis. PIVKA-II, reported as a highly specific tumor marker for HCC, was thought to be less available for detection of early HCC occurring in the course of liver cirrhosis in comparison with AFP. Carcinoembryonic antigen (CEA), a most popular and useful tumor marker for cancer of digestive organs, was frequently positive in sera of colorectal cancer patients who had no subjective complaint or physical sign. This experience supported employment of CEA as a routine screening test for colorectal cancer. A survey of routine examinations of serum CA 19-9 for a period of one month in the clinical laboratory of our hospital proved that 92% of the positive cases of low-level CA 19-9 from 37 U/ml to 75 U/ml were noncancerous. This result indicated that the cut-off value of 37 U/ml employed for serum CA 19-9, which had been evaluated as a specific and highly sensitive tumor marker for pancreatic cancer and bile duct cancer, was too low. Accordingly, it was thought necessary to investigate a change of cut off value and reevaluate CA 19-9 for pancreatic cancer and bile duct cancer in comparison with other tumor markers of carbohydrate antigen such as CA 50, sialyl SSEA-1. From our experience in the use of tumor markers, the combination assays of fetal protein such as AFP, CEA, basic fetoprotein (BFP) and carbohydrate antigen, such as CA 19-9 and CA 50, for routine examination of tumor marker, are recommended for effective screening of cancer of digestive organs.     

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.     

Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy.

BACKGROUND: The objective of this study was to identify clinical, biochemical, ultrasound, and/or pathologic parameters capable of predicting survival in a cohort of patients with well compensated cirrhosis and small hepatocellular carcinoma (HCC) who were treated with percutaneous ethanol injection (PEI). METHODS: The study group included 111 patients with Child--Pugh Class A cirrhosis and with one (93 patients) or two (18 patients) HCC nodules measuring < 5 cm in greatest dimension. All patients underwent multisession PEI. The prognostic values of pretreatment and post-treatment variables were analyzed using the Kaplan-Meier method. RESULTS: The overall 3-year and 5-year survival rates of 62% and 41%, respectively, were not influenced by age, gender, duration of chronic hepatitis, serum albumin, prothrombin time ratio, total bilirubin, gamma-glutamyl transferase, hepatitis B surface antigen, antihepatitis C virus, HCC size, HCC ultrasound pattern, HCC histologic or cytologic grading, greatest spleen dimension, esophageal varices, or ascites. Levels of alpha-fetoprotein (AFP) > 14 ng/mL (P < 0.006), alanine aminotransferase > 75 IU/L (P < 0.04), and aspartate aminotransferase > 80 IU/L (P < 0.009) and platelet count < 92 x 10(9)/L (P < 0.02) before treatment were independent predictors of decreased survival. Among post-treatment parameters, AFP levels 6 months after PEI > 13.3 ng/mL (P < 0.003) and HCC recurrence in another segment of the liver (P < 0.04) were linked to decreased survival in univariate analysis. CONCLUSIONS: Among patients with Child--Pugh Class A cirrhosis with small uninodular or binodular HCC who are treated with multisession PEI, those with elevated serum AFP and transaminase levels and low platelet count before treatment are characterized by decreased survival. During follow-up, intrahepatic recurrence of the tumor is the main factor affecting survival.     

肝癌患者围手术期外周血甲胎蛋白mRNA表达与术后复发的关系

背景与目的:甲胎蛋白(alpha-fetoprotein,AFP)mRNA是检测肝癌患者外周血中癌细胞常用的标志物。本研究探讨肝癌患者围手术期的外周血中AFPmRNA表达与术后复发的关系。方法:应用巢式PCR和Taq Man MGB探针法PCR定量技术,检测56例肝细胞癌患者术前和术后外周血、15例良性肝占位性病变合并肝硬化患者外周血以及30例健康志愿者外周血AFP mRNA的表达情况。结果:肝癌患者术前外周血AFP mRNA的阳性率为42.9%(24/56),高于良性肝占位合并肝硬化患者的13.3%(2/15)和健康对照的10.0%(3/30),其差异均有统计学意义(P=0.035,P=0.002)。术前AFP mRNA的表达与肿瘤有无肉眼及镜下血管侵犯的相关性有统计学意义(P=0.029,P<0.001)。AFP mRNA阴性患者1、2、3年生存率及无瘤生存率均比AFP mRNA阳性患者术后高(P=0.003,P=0.039)。Cox多因素分析结果显示术前外周血AFP mRNA阳性是预测术后复发的独立因素(P=0.018)。术后患者外周血AFP mRNA的阳性率为37.5%(21/56),术后AFP mRNA的表达与患者各项临床病理特征、预后以及术前AFP mRNA水平的相关性均无统计学意义。结论:肝癌患者术前外周血中AFP mRNA阳性者比AFP mRNA阳性者肿瘤侵袭性更强,术后可能更易复发。