title: 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.
  
  
  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.
authors.affiliation: Department of Pathology "Iuliu Hatieganu", Cluj-Napoca, 2Angiogenesis Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, 3Department of Pathology, 4Department of Surgical, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania E-mail : cioca_andre@yahoo.com.
authors.forename: Andreea
authors.initials: A
authors.lastname: Cioca
authors.forename: Anca
authors.initials: A
authors.lastname: Cimpean
authors.forename: Raluca
authors.initials: R
authors.lastname: Ceausu
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Fit
authors.forename: Teodor
authors.initials: T
authors.lastname: Zaharie
authors.forename: Nadim
authors.initials: N
authors.lastname: Al-Hajjar
authors.forename: Vlad
authors.initials: V
authors.lastname: Puia
authors.forename: Marius
authors.initials: M
authors.lastname: Raica
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors