Crosstalk between EGFR and p53 in Hepatocellular Carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. 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. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent 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 staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

Down-Regulation of MiR-193a-3p Dictates Deterioration of HCC: A Clinical Real-Time qRT-PCR Study

“…Studies have already suggested that nm23 with pro-oncogenic potential was involved in hepatocarcinogenesis [ 31 ], and that its expression in tumor tissues was correlated with metastasis and survival in HCC, which may also be an indicator for prognosis [ 32 ]. Studies also showed that overexpression of p53 contributed to the hepatocarcinogenesis and more advanced stage of HCC [ 33 ]. As we found there was significant difference of miR-193a-3p expression in nm23 as well as p53-positive and -negative HCC patients in the current study, miR-193a-3p may be a pro-oncogenic potential indicator, as nm23 and p53 are in HCC.…”

Efficacy of bevacizumab combined with erlotinib for advanced hepatocellular carcinoma: a single-arm meta-analysis based on prospective studies

“…HCC patients manifest conspicuously elevated levels of vascular endothelial growth factor (VEGF) expression and frequently show increased co-expression of TGF-alpha and EGFR [8], leading to active and massive cell proliferation because TGF-alpha, epidermal growth factor receptor (EGFR) and its ligand EGF play important roles in cell proliferation [9]. Erlotinib, a tyrosine kinase inhibitor that down-regulates VEGF, was reported to be efficacious in advanced HCC [10, 11].…”

The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment

“…Other clinical studies evaluated the co-expression of mutant p53 and EGFR mutations/overexpression in different tumours, suggesting a correlation with poor prognosis and a lack of response to tyrosine kinase inhibitors, chemotherapy and radiotherapy in non-small cell lung cancer, head and neck, and hepatocellular malignancies [81][82][83][84]. However, the clinical role of TP53 mutational status in CRC is still controversial.…”