Crosstalk between EGFR and p53 in Hepatocellular Carcinoma


Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a highmortality. Most patients present with late stage disease, when the treatment options are limited to systemicchemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC,and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and
Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathologicaldata including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosisand chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields wereselected for each sample and all the tumor cells within each microscopic field were counted, and then the positivepercent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal.The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane stainingwas observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense darkbrown staining delineated the membrane. To determine the relationship between EGFR expression and p53, weperformed double staining in the same HCC specimens.
Results: By immunohistochemical staining, p53 proteinwas detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity ofp53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked tohistological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFRintensity (p=0.014).
Conclusions: Our results suggest that overexpression of p53 and EGFR plays an importantrole in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuablepredictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.