Expression And Significance Of Type Ⅱ Ground-Glass Hepatocytes In HBV-Related HCC Adjacent Tissues

Background:Primairy hepatocellar carcinoma(HCC) is a common cancer with high degree of malignance in the digestive system, and the treatment effect is not ideal. The development of HCC is concealed, there are non-specific clinical manifestation in the early stage and it becomes advanced quickly with poor prognosis. So far,the clinician generally considered that the hepatitis B virus(HBV) infection is associated with HCC. In China, in particular, chronic hepatitis B virus is the most etiologic reason in many pathogenic factors of HCC.the pathogenesis of HBV-related HCC previously proposed including the inflammation and regeneration, functional gene product of HBV, HBV genome insertion mutation, etc. In recent years, some foreign scholars have found that the type Ⅱ ground glass hepatocytes(GGHs) is highly expressed in the adjacent to carcinoma and represent the precancerous lesions of the HBV-related HCC. Type Ⅱ GGHs contain pre-S2 mutants, endoplasmic reticulum(ER) stress-dependent and-independent pathways induced by pre-S2 mutants lead to oxidative DNA damage, genomic instability, cell cycle progression and cell proliferation, these mentioned result in type Ⅱ GGHs growth advantage, and ultimately the formation of HCC. In addition, type Ⅱ GGHs contain X protein(HBx), which plays an important role in the duplication of HBV and HBV-induced liver disease(including hepatitis, cirrhosis and HCC). Experimental studies have found that transgenic mice harboring either HBx or pre-S2 mutant plasmids developed HCCs, ultimately. In addition, 5%-10% 0f type Ⅱ GGHs co-express pre-S2 mutant and HBx, and exhibit enhanced oncogenic and tumorigenesis in transgenic mice. Objective:In this study, the expression of type Ⅱ GGHs was assessed by immunohistochemistry in HBV-related HCC tissues, in corresponding tumor adjacent tissues and in distal liver tissues. By comparison of its expression, this research was aimed to exploring the features of type Ⅱ GGHs in the above tissue as well as the relationships between the clinical parameters. Methods:The study used immunohistochemical staining methods(Elivision two-step), detected the expression level of type Ⅱ GGHs in the 48 HCC tissues, corresponding tumor adjacent tissues and distal liver tissues from patients with HBV-related HCC who underwent curative surgical resection performed by single treatment group, and analyse the relationships between type Ⅱ GGHs and clinical parameters(such as age, histopathological grading, liver cirrhosis, microvascular invasion, the greatest tumor diameter, serum HBV-DNA load, serum HBe Ag status, serum TBIL, serum albumin, AFP) of the patients with HCC. Results:1.The expression rate of type Ⅱ GGHs in tumor adjacent tissues(from the tumor edge 2-3 cm) was 87.5%(42/48), while it was 16.7%(8/48) in distal liver tissues(from the tumor edge more than 4 cm), the most notable GGHs was typeⅠ and mixed type(the typeⅠand type Ⅱ GGHs can observe in the same view) in distal liver tissues, type Ⅰ GGHs accounted for 12.5%(6/48) and mixed type GGHs accounted for 54.2%(26/28); On the contrary, GGHs was not expression in any HCC tissues.2.type Ⅱ GGHs exhibited clusters distribution. The expression of type Ⅱ GGHs in tumor adjacent tissues was not related to the clinical parameters such as age, histopathological grading, microvascular invasion, the greatest tumor diameter, serum HBe Ag status, serum TBIL, serum albumin. However, The expression of type Ⅱ GGHs was related with serum AFP level, serum HBV-DNA load and with or without liver cirrhosis, the difference was statistical significance. Conclusion:Type Ⅱ GGHs expressed highest levels in tumor adjacent tissues, lower levels in distal liver tissues, and no expression in HCC tissues. The expression of type Ⅱ GGHs in tumor adjacent tissues was closely related with serum AFP level, serum HBV-DNA load and with or without liver cirrhosis.