The prognostic role of angiogenesis, lymphangiogenesis and vasculogenic mimicry in hepatocellular carcinomas treated with transplantation

Aim: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy in adults. There is some data about the decisive role of angiogenesis in carcinogenesis and progression of HCC which is an hypervascular tumor. The aim of this study is; to determine the amount of angiogenesis numerically and to study different vascularization patterns like lymphangionesis and vasculogenic mimicry (VM) by morphometric and immunhistochemical methods in tumors and to examine the prognostic role of vascularization in the postoperative outcome of HCC, after transplantation. Material and Methods: In our study; 60 cases with the HCC which was treated with the transplantation were investigated. Intratumoral angiogenesis was highlighted by anti- CD34 and anti-CD105 antibodies, and lymphangiogenesis was evaluated by anti-D2-40 antibody by using immunuhistochemistry in tissue microarray slides. The amount of vessels were identified as area of vessels and number and area of objects per unit (mm2) with image analyze programme. Tubuler type VM was evaluated with hematoxylin and eosin slides. Patterned VM in HCC was identified by the laminin antibody. The morphologic and immunhistochemical study results were analysed statistically to evaluate the relation with prognostic factors and survival. Results: We found tubular type VM in 16 cases and patterned VM in 11 cases (n=60). We showed both type of VM in HCC. But no significant result could be found statistically between VM presence and the survival and prognostic factors. We found the statistically significant relationship with number of objects per unit in CD34 positive vessel analysis and overall survival. The number of objects per unit in CD34 positive vessel analysis was significantly lower in patiens with worse outcome (p=0,006). But there is no relation between the number of objects per unit in CD34 positive vessel analysis and tumor size, number of tumor nodules, pathologic T stage, tumor grade, vascular invasion and patients? age, CHILD score, MELD score and recurrence. Besides that, we found the expression of CD105 lower than the CD34 expression but no significant correlation between them. We showed the lymphatics in tumor parenchyma and in fibrous capsule surround the tumor nodules. Conclusion: Our data supports that there is different and independent vascularization patterns in HCC. But the negative prognostic and therapeutic effects of these mechanisms and increase in vascularity could not be proved. We could only show the increase in vascularization detected by CD34 was related with better prognosis. We think image analysis method used in this study is affective but may not ideal. İmage analyze programme and stereological methods need to be correlated within TMA sections and rutine slides. But our results were affected by the selection of cases which were mostly in early stage and low recurrent tumor incidence in our series. For this purpose; there is need for the widespread studies having an advance stage and less differentiated tumors.