| Purpose:Our country is a big country of the liver disease, Chinese everyyear has 130,000 sufferers to die of prima ry hepatica carcinoma(HCC),accounting for 45% of the globa l HCC death total amount.So one of ourimportant med ical missions is how to improve achievement ratio of HCCdia gnosis.Alpha fetoprotein(AFP), a specific tumor marker of HCC, has beenapplying to dia gnosing HCC for more tha n 20 years in the clinic. AFP is one ofimportant index for dia gnosing HCC now.But in recent years, AFP has beenfound with high value in some non-ma ligna nt liver and galls disease, whichcoincide with the HCC to some degree. And more important, in parts of HCCsufferers AFP presents the low value even nega tive. It was reported that nega tiveratio of AFP in HCC can amount to 30% above.To dia gnose HCC by AFP aloneas the tumor marker,weeasily met missed dia gnosis and misd ia gnosis. So thetrend to improve the fina l dia gnosis ratio of HCC is to detect more tha n one of HCC tumor markers combinedly. This article supposed to detect AFP, GGT-Ⅱand sICAM-1 consociated ly in HCC sufferers'plasma or sera, and to prove thetriple consociation detection can enhance the fina l dia gnosis ratio moreobviously tha n AFP alone.Method:We collected altogether 220 blood samples,includ ing 46 cases ofHCC,18 cases of liver metastatic carcinoma,38 cases of liver benign tumor,42cases of hepatic cirrhosis,30 cases of hepatitis and 46 cases of norma l controls,and measured plasma and sera AFP,GGT-Ⅱ, sICAM-1with fluorescent enzymelinked immunosorbent assay,vertica l polyacrylamide gelgradient electrophoresisand double antibody enzyme linked immunosorbent assay.Result:1.It was demonstrated that there was no correla tion betweenAFP,GGT-Ⅱand sICAM-1in 30 HCC patients(P>0.05). That is the same to 220patients and norma l controls.This indica te that the three tumor markers areindependent and can be measured combinedly.2.It was reported that sICAM-1can go up obviously when HCCmetastasized to liver outside, so we contranst it in patients with metastasis withno metastasis in HCC group.We found plasma sICAM-1concentration was muchhigher in patients with metastasis tha n no metastasis, and sICAM-1 positive ratioin the former(93.8％)was also higher tha n the latter(15.3％).3. To measure AFP, sICAM-1and GGT-Ⅱrespectively, the positive rate ofthe HCC was only 76%,68% and 92%, and the specificity was 95%,90% and86%. We can see positive rate of HCC by measuring the three markerscombinedly was obviously higher tha n by respectively, even though specificitywas slightly decreased. At the same time we can also see, the accuracy was 85%,78% and 89%,the probability of missed dia gnosis was 10.26％,15.32％and4.24％,and the Youden`s index was 0.71,0.58 and 0.78 when AFP,sICAM-1and GGT-Ⅱwere measured respectively. But the probability of missed dia gnosis ,the accuracy and the Youden`s index was 1.91％,93％and 0.86 when they weremeasured consociated ly. By X2 test for probability of missed dia gnosis whenthey were measured consociated ly compared to that respectively, value P wasless tha n 0.01 and has significa nt statistica l difference.But there was nosignifica nt difference of accuracy between them.Discussion:AFP as a tumor marker has been use to dia gnose hepatocellularcarcinoma(HCC) clinica lly as a serologic detection for more tha n 20 years .It isthe most commonly used and most valuable serologic dia gnosis index .Thepositive rate of AFP used alone is between 0.4-0.8.While the AFP concentrationof part hepatic carcinoma is very low or negtive ,it result in high rate of misseddia gnosis. In this experiment the positive rate of AFP for dia gnosing HCC is76%,the probability of missed dia gnosis is 10.26%.So it can't used as a standardof exclusive dia gnosis.From our observed result we can see the sensitivity of GGT-Ⅱis thehighest(9 2%),the sensitivity of AFP is lower(76%), and the sensitivity ofsICAM-1is the lowest(6 8%).The specificity of AFP is 95%,the specificity ofsICAM-1is 86%,and the specificity of GGT-Ⅱis 90%.The probability ofmissed dia gnosis of GGT-Ⅱis 4.24% ,AFP`s is 10.26%, sICAM-1`s is 15.32%.The accurate rate of GGT-Ⅱis 89%,AFP`s is 85%, sICAM-1`s is 78%.TheYouden`s index of GGT-Ⅱis 0.78,AFP`s is 0.71, sICAM-1`s is 0.58.Synthetic estimated, GGT-Ⅱhas higher sensitivity and accurate rate andhas lower probability of missed dia gnosis ,but its specificity is lower tha n AFPand sICAM-1.AFP has higher specificity and accurate rate ,but its sensitivity islower and its rate of missed dia gnosis is higher. The sensitivity of sICAM-1 islower and its rate of missed dia gnosis is highest,but its specificity is good and accurate rate is not very low.But if we divide HCC patients into two groups:extrahepatic metastatic group and non-extrahepatic metastatic group, thesensitivity of sICAM-1 is 93.8% in extrahepatic metastatic group,and itssensitivity is 15.3% in non-extrahepatic metastatic group.There is no notablestatistics difference(P>0.05)between AFP,GGT-Ⅱand whether the extrahepaticmetastatic exist or not.It indica tes that sICAM-1has important significa nce tojudge if HCC patients haveextrahepatic metastatic.It is in favour of clinica llyfingd ing extrahepatic focus in early stage and giving active treatment.In the 11 AFP negtive HCC patients, 3 cases of them have positive sICAM-1,8 cases have positive GGT-Ⅱ,the positive detection rate of any of them is85%, the positive detection rate of both of them is 86%.It indica te sICAM-1andGGT-Ⅱhave well supplementary effect for the HCC patients whose AFP isnegtive .It can reduce the probability of missed dia gnosis of AFP .So it suggestssimultaneous determination of AFP, sICAM-1and GGT-Ⅱis necessary.In 18 cases of who have hepatic metastatic carcinoma, AFP are nega tive,only 1 case have positive sICAM-1 and 12 patients's GGT-Ⅱis positive.Itsuggest that its specificity is low ,if GGT-Ⅱis used to dia gnose HCC alone .Weshould use simultaneous determination with other tumor marker to increase thespecificity of the dia gnosis of HCC.The sensitivity of simultaneous determination of AFP,sICAM-1and GGT-Ⅱis raised to 96%,while the sensitivity of single detection is 68%-92%.But thespecificity is reduced to 90％,while the specificity of single detection is 86%-95%.The probability of missed dia gnosis is markedly reduced to 1.91%, whilethe probability of missed dia gnosis of single detection is 4.24%～15.32%.It hassignifica nt statistics difference and can increase detection rate , decrease falsenega tive rate and false positive rate.The accuracy rate does not marked change(P>0.05). It indica tes that simultaneous determination does not decreasethe accuracy rate of HCC dia gnosis.Synthetic estimated, simultaneous determination of AFP,sICAM-1andGGT-Ⅱcan increase the sensitivity and accuracy ,and can decrease theprobability of missed dia gnosis .But the specificity are decreased.Conclusion:GGT-Ⅱwhich is one of hepatica carcinoma markers isdetected in 92% of HCC patients.This is better tha n 76% of AFP detected alone.Specificity of GGT-Ⅱ,90%,is slightly less tha n that of AFP(95%).Concentrationof sICAM-1in HCC patients whose carcinorma has transferred outside of liver ismore than that of not transferred.This indica ted that is significa nt for judgewhether cancer is metastasized in HCC patients to detected the concentration ofsICAM-1in plasma.Detection of AFP, GGT-Ⅱand sICAM-1consociated ly canenhance the sensitivity and accuracy of dia gnosing HCC, and lower probabilityof missed dia gnosis.So it is necessary to detect the markers of HCCconsociated ly. Purpose:HCC (hepatocellular carcinoma) is a kind of common cancer,it`smortality was the 3rd of ma le in the whole world,and it was the 5th of thefema le.There are more than 1000,000 pantients die of this in our country everyyear.Surgical resection is still the best way of the treatment of HCC,till now.Butthe postoperative recurrence and metastasis is one of the ma in reasons ofinfluence on long-term prognosis.The high rates of recurrence and metastasis isthe result of the undiscovered micrometasta tic lesion preoperative ordissemination into blood of the carcinoma cells intraoperative.Recent years,thescholars searched for the carcinoma cells in the blood circulation of the patientsof HCC with the technology of sensitive reverse transcription polymerase chainreaction(RT-PCR),in order to find the micrometasta tic lesion earlier. MessengerRNAs (mRNAs) of AFP and albumin are common markers for detecting themicrometastasis of hepatocellular carcinoma.We contrast the AFP mRNA`sepression level in the blood of patients of HCC and normal controls by dectctingwith nested RT-PCR.To study the relationship between the result and themicrometastasis of hepatocellular carcinoma.Method:1.We divided 40 HCC patients into single nodule group,10 cases;≥2nodules group,10 cases; dista nt metastasis group,20 cases. 2.We also divided these patients into the tumor`s dia meter≤5cm,15 cases;>5cm,25 cases.3.40 normal controls. We detected the AFP mRNA`s epression level in theblood of these groups with nested RT-PCR.Results:1.The positive rate of AFPmRNA in 10 patients with single nodule of HCCwas 30%(3/10); the positive rate of patients in 10 patients with≥2 nodules ofHCC was 40%(4/10); the positive rate of AFPmRNA in 20 patients withmetastatic lesions of HCC was 90%(18/20).2.The positive rate of AFPmRNA in 15 patients with the tumor`s dia meter≤5cm was 53.3%(8/15);the positive rate of AFPmRNA in 25 patients with thetumor`s dia meter >5cm was 76%(19/25);3. The positive rate of AFPmRNA in 40 normal controls was 5%(5/40).Discussion:The cells that express AFP enter the blood during the tumormetastasis ,while the liver cells carcinogenesis ,and they become the markers ofthe micrometasta tic tumors.The free RNA can`t exist independently because ofthere is RNase in periphera l blood. Therefore,detection of AFPmRNA justmea ns there`re complete cell that produce AFP exist in periphera l blood.Our study showed,the positive rate of AFPmRNA in HCC patients was62.5%(25/40),a nd by the tumor progress,the positive rate increase dsignifica ntly( single nodule 30%,≥2 nodules 40% and that with metastaticlesions of HCC was 90%,P<0.05).The degree of the tumor progression relateswith the factors like the tumors` size,numbers,etc.This was in good agreementwith the other results of our study.That was the positive rate of AFPmRNA wasintimately related with the tumors` size,numbers(P<0.05).One of the influencefactors of the carcinoma cells dissemination intra-and extrahepatic was the size of the tumor,when the tumor`s size increase d,the carcinoma cells exfolia ted fromthe prima ry foci and enter the periphera l blood easily.Conclusion: The positive rate of AFPmRNA in HCC patients` periphera lblood intimately relates with the tumors` size,numbers and the degree of thetumor progression.It is a sensitive index that can show that if there are carcinomacells exist in the HCC patients` periphera l blood.It has very important clinicalsignifica nce on the early dia gnosis of HCC and the detection of themicrometastasis of hepatocellular carcinoma.
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