The Expression And Significance Of Glypican-3,p16,IGFBP-3,WWOX In Hepatocellular Carcinoma

ObjectiveHepatocellular carcinoma(HCC) is one of the most common malignant tumors in China.From 1900,the morbidity ranked the 2nd respectively among all types of malignant tumors.The mortality ranked the 3rd or 2nd respectively among all types of malignant tumors.HCC is characteristic of latent and quick development and early metastasis.Its five year-survival rate is very lower,and about 2/3 patients have been in the later stage when they had the first examination.The early detection of HCC is critical for its effective treatment.The most important tumor marker for HCC is alpha-fetoprotein(AFP).However,30-40%of HCC patients were negative for AFP.Therefore,looking for new and effect tumor markers which express in HCC patients is important.Our laboratory have detected the expression of Glypican-3 (GPC3),P16,Insulin-like Growth Factor Binding Proteins-3(IGFBP-3),WW domain-containing oxidoreductase(WWOX) of HCC and adjacent non-cancerous tissues by using RT-PCR.The GPC3-positive expression of HCCs was notably higher than that of all adjacent non-cancerous tissues.While,the others results were contrary.The purpose of this study is to detect expression of GPC3,p16,IGFBP-3,WWOX by immunohistochemistry method in HCC and all adjacent non-cancerous tissues and to investigate the relationship between GPC3,p16,IGFBP-3,WWOX expression and clinicopathologic characteristics such as gender,age of the patient, serum AFP and HBsAg,cirrhosis,size and differentiation of tumor,growth pattern and clinical stage.The aim is to investigate their clinical diagnostic significance.MethodsImmunohistochemistry was used to detect the expression of GPC3,p16,IGFBP-3,WWOX in 60 specimens of HCC and adjacent non-cancerous tissues and to assess the diagnostic value of them in HCCs.The expression of them was then correlated to the clinicopathological characteristics.Then 40 liver needle biopsy specimens of hepatocellular carcinomas were immunohistochemically examined for expression of GPC3. Results1.GPC3 was expressed in 45(75%) resection cases and in 33(82.5%) liver needle biopsy specimens of hepatocellular carcinomas,whereas all adjacent non-cancerous tissues were GPC3-negtive.When GPC3 staining was positive in HCCs,it was mainly membranous and cytoplasmic.The GPC3 positive expression was graded by percentage of positive cells and intensity of staining as diffuse and strong,diffuse and weak,focal and strong,focal and weak.There were no relationship between GPC3 expression and clinicopathologic characteristics.2.p16 was expressed in 55%(33/60) of HCC,86.7%(52/60) in adjacent non-cancerous tissues.The positive rate in adjacent non-cancerous tissues was much higher than that in HCC(p＜0.05).p16-positive expression was mainly diffusely cytoplasmic.The expression was correlate with tumor differentiation(p＜0.05).3.IGFBP-3 was expressed in 53.3%(32/60) of HCC,70.2%(43/60) in adjacent non-cancerous tissues.The positive rate in adjacent non-cancerous tissues was much higher than that in HCC(p＜0.05).IGFBP-3-positive expression was mainly cytoplasmic and membranous.There were no relationship between positive expression and clinicopathologic characteristics.4.No positive expression was discovered in HCCs or adjacent non-cancerous tissues.ConclusionGPC3-immunohistochemistry was significantly much more specific and sensitive for hepatocellular carcinomas,which is possible to become a new pathological diagnostic marker of HCC.The positive expression rates of p16 and IGFBP-3 in HCCs is were significantly lower than those of all adjacent non-cancerous tissues,which indicate that their losing might play an important role in the pathogenesis of HCC.A combination of these molecular markers might result in further increases in sensitivity and specificity in the detection of early HCC.