تغییرات بیان ژنهای P53 ، Cyclin-D1 ، RB1 ، c-Fos ، N-ras در هپاتوسلولار کارسینوما در ایران

Background: Hepatocellular carcinoma is the most common primary malignant tumor of the liver. The effect of some genes especially those involved in cell cycle regulation have been shown in the development of this cancer in several studies but there are some controversies about them yet. Materials and methods: The paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during a period of 2 years (2000-2001). Using immunohistochemistry method (avidin-biotin-peroxidase), they were stained for detection of p53, cyclin D1, RB1, c-fos and N-ras proteins. Results: The mean (SD) age of the subjects was 60.5612.52 years. Six (24%), 5(20%), 12(48%) and 2(8%) were positive for p53, cyclin D1, C-fos and N-ras, respectively. Twenty-two (88%) samples had alterations in the G1 cell-cycle checkpoint proteins (RB1 or cyclin D1). P53 positive cases showed a higher (9 times) risk of being positive for RB1 gene comparing with p53 negative samples. RB1 loss of expression in association with p53 over-expression has been observed in 4(66.7%) of samples. Loss of expression of RB1 was seen in all cyclin D1 positive, 20(90.9%) N-ras negative, and 11(50%) C-fos positive cases. Comparing cyclin D1 positive cases with the negative ones, the former group showed a higher (2.85 and 4.75 times) risk of being positive for c-fos and N-ras genes. Conclusion: The development of mutation in p53, RB1 and c-fos genes appear to have a key role in the carcinopathogenesis of HCC in Iran. Also a significant association between simultaneous mutations of these genes during development of HCC is likely.