Avaliação imunoistoquímica da via de sinalização Hedgehog no carcinoma hepatocelular e correlação com fatores prognósticos

Abstract

Introduction: hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm in the liver, with an increase in its incidence and mortality with advancing age. This neoplasm is closely associated with hepatic cirrhosis as the underlying disease, which has its main etiology in chronic viral infections, such as hepatitis B virus (HBV) and hepatitis C virus (HCV), responsible for approximately 85% of cases, in addition to liver injury caused by alcohol. In addition to the various signaling pathways already described in hepatocarcinogenesis, the Hedgehog pathway can be highlighted, since it plays an important role in cell proliferation and differentiation during the embryonic period. Objective: this study aims to evaluate the expression of binding protein Sonic Hedgehog (Shh) in HCC samples obtained from patients submitted to liver transplantation at the Clinical Hospital of the Federal University of Minas Gerais (HC-UFMG) and to correlate its marking indices with clinical and morphological prognostic factors. Methodology: immunohistochemical evaluation of Shh binding protein expression was performed in 36 CHC samples stored in the HC-UFMG pathology department, as well as expression in the adjacent cirrhotic parenchyma. The clinical and morphological data of all the cases were obtained through a review of the medical records, as well as review of original slides and histopathological reports, filed in the HC-UFMG database. Correlation of Shh expression with MELD score, alpha-fetoprotein levels, degree of tumor differentiation, presence or absence of angiolymphatic invasion, number of tumor nodules identified, size of largest nodule, and etiology of concomitant cirrhosis disease were performed. Results: two morphological factors identified in conventional HE examination (degree of tumor differentiation and vascular invasion) were directly correlated with the intensity of Shh protein expression (p = 0.014 and p = 0.003, respectively). The other variables did not show a statistically significant correlation with the tumor or parenchymal expression of SHH (p> 0.05). Discussion: the direct correlation between the degree of tumor differentiation and the presence of vascular invasion with the strong cytoplasmic expression of Shh allows us to infer that this expression is more evident in tumors with greater aggressiveness potential, since these morphological parameters are considered fundamental for prognostic establishment. Conclusion: the strong cytoplasmic expression of Shh protein in hepatocellular carcinoma can be considered as a factor associated with worse prognosis. The identification of this expression allow us to study and consider the use of chemotherapeutic agents that act blocking the Hedgehog pathway for the clinical treatment of HCC.