Immunohistochemical analysis of p53, cyclinD1, RB1, c-fos and N-ras gene expression in hepatocellular carcinoma in Iran.
OBJECTIVE
To study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma.


METHODS
Paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method (avidin-biotin-peroxidase) for detection of p53, cyclinD1, RB1, c-fos and N-ras proteins.


RESULTS
Six (24%), 5 (20%), 12 (48%) and 2 samples (8%) were positive for p53, cyclinD1, C-fos and N-ras expression, respectively. Twenty-two (88%) samples had alterations in the G1 cell-cycle checkpoint protein expression (RB1 or cyclinD1). P53 positive samples showed a higher (9 times) risk of being positive for RB1 protein than p53 negative samples. Loss of expression of RB1 in association with p53 over-expression was observed in 4 (66.7%) of 6 samples. Loss of expression of RB1 was seen in all cyclinD1 positive, 20 (90.9%) N-ras negative, and 11 (50%) C-fos positive samples, respectively. CyclinD1 positive samples showed a higher (2.85 and 4.75 times) risk of being positive for c-fos and N-ras expression than cyclinD1 negative samples.


CONCLUSIONS
The expression of p53, RB1 and c-fos genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma.
Moghaddam
S J
SJ
Shaheed Beheshti University of Medical Sciences, Research Center for Gastroenterology and Liver Disease, Tehran 19857, Iran.
Haghighi
E N
EN
Samiee
S
S
Shahid
N
N
Keramati
A R
AR
Dadgar
S
S
Zali
M R
MR
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000209:etiology / Q000235:genetics*; D019938:Cyclin D1 / Q000032:analysis*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D016160:Retinoblastoma Protein / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D016760:Proto-Oncogene Proteins c-fos; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1