DOI QR코드

DOI QR Code

Tissue Microarray Immunohistochemical Profiles of p53 and pRB in Hepatocellular Carcinoma and Hepatoblastoma

  • Azlin, Abdul Hadi (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Looi, Lai Meng (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Cheah, Phaik Leng (Department of Pathology, Faculty of Medicine, University of Malaya)
  • 발행 : 2014.05.15

초록

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

키워드

참고문헌

  1. Azechi H, Nishida N, Fukuda Y, et al (2001). Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology, 60, 346-54. https://doi.org/10.1159/000058531
  2. Brodeur GM (1995). Genetics of embryonal tumours of childhood: retinoblastoma, Wilms' tumour and neuroblastoma. Cancer Surv, 25, 67-99.
  3. Chen BK, Singh H, Krishnan R, Fong SH (2004). Comparison of the expression of beta-catenin in hepatocellular carcinoma in areas with high and low levels of exposure to aflatoxin B1. J Surg Oncol, 86, 157-63. https://doi.org/10.1002/jso.20051
  4. Chittmittrapap S, Chieochansin T, Chaiteerakij R, et al (2013). Prevalence of aflatoxin induced p53 mutation at codon 249 (R249s) in hepatocellular carcinoma patients with and without hepatitis B surface antigen (HBsAg). Asian Pac J Cancer Prev, 14, 7675-9. https://doi.org/10.7314/APJCP.2013.14.12.7675
  5. Choi SW, Hytiroglou P, Gellar SA, et al (1993). The expression of p53 antigen in primary malignant epithelial tumors of the liver: an immunohistochemical study. Liver, 13, 172-6.
  6. Farshid M, Hsia CC, Tabor E (1994). Alterations of the RB tumour suppressor gene in hepatocellular carcinoma and hepatoblastoma cell lines in association with abnormal p53 expression. J Viral Hepat, 1, 45-53. https://doi.org/10.1111/j.1365-2893.1994.tb00061.x
  7. Goldblum JR, Bartos RE, Carr KA, Frank TS (1993). Hepatitis B and alterations of the p53 tumor suppressor gene in hepatocellular carcinoma. Am J Surg Pathol, 17, 1244-51. https://doi.org/10.1097/00000478-199312000-00005
  8. Hagn F, Lagleder S, Retzlaff M, et al (2011). Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53. Nat Struct Mol Biol, 18, 1086-93. https://doi.org/10.1038/nsmb.2114
  9. Hsu IC, Metcalf RA, Sun T, et al (1991). Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature, 350, 427-8. https://doi.org/10.1038/350427a0
  10. Hui AM, Li X, Makuuchi M, Takayama T, Kubota K (1999). Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma. Int J Cancer, 84, 604-8. https://doi.org/10.1002/(SICI)1097-0215(19991222)84:6<604::AID-IJC11>3.0.CO;2-Y
  11. Huynh H (2004). Overexpression of tumour suppressor retinoblastoma 2 protein (pRb2/p130) in hepatocellular carcinoma. Carcinogenesis, 25, 1485-94. https://doi.org/10.1093/carcin/bgh154
  12. Ishak KG, Anthony PP, Sobin LH (1994). Histological typing of tumours of the liver. World Health Organization International Histological Typing of Tumours, 2nd ed. Berlin: Springer-Verlag.
  13. Ishak KG, Glunz PR (1967). Hepatoblastoma and hepatocarcinoma in infancy and childhood. Report of 47 cases. Cancer, 20, 396-422. https://doi.org/10.1002/1097-0142(1967)20:3<396::AID-CNCR2820200308>3.0.CO;2-O
  14. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  15. Kennedy SM, Macgeogh C, Jaffe R, Spurr NK (1994). Overexpression of the oncoprotein p53 in primary hepatic tumors of childhood does not correlate with gene mutation. Hum Pathol, 25, 438-42. https://doi.org/10.1016/0046-8177(94)90114-7
  16. Lim GCC, Rampal S, Halimah Y (2008). Cancer Incidence in Peninsular Malaysia 2003-2005. The Third Report of the National Cancer Registry. National Cancer Registry, Ministry of Health Malaysia. Kuala Lumpur.
  17. Litten JB, Tomlinson GE (2008). Liver tumors in children. Oncologist, 13, 812-20. https://doi.org/10.1634/theoncologist.2008-0011
  18. Milanes-Yearsley M, Hammond ME, Pajak TF, et al (2002). Tissue micro-array: a cost and time-effective method for correlative studies by regional and national cancer study groups. Mod Pathol, 15, 1366-73. https://doi.org/10.1097/01.MP.0000036345.18944.22
  19. Moudgil V, Redhu D, Dhanda S, Singh J (2013). A review of molecular mechanisms in the development of hepatocellular carcinoma by aflatoxin and hepatitis B and C viruses. J Environ Pathol Toxicol Oncol, 32, 165-75. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2013007166
  20. Pan H, Fu X, Huang W (2011). Molecular mechanism of liver cancer. Anticancer Agents Med Chem, 11, 493-9. https://doi.org/10.2174/187152011796011073
  21. Ruck P, Xiao JC, Kaiserling E (1994). p53 protein expression in hepatoblastoma: an immunohistochemical investigation. Pediatr Pathol, 14, 79-85. https://doi.org/10.3109/15513819409022028
  22. Schaff Z, Sarosi I, Hsia CC, Kiss A, Tabor E (1995). p53 in malignant and benign liver lesions. Eur J Cancer, 31, 1847-50. https://doi.org/10.1016/0959-8049(95)00380-2
  23. Shiraha H, Yamamoto K, Namba M (2013). Human hepatocyte carcinogenesis (review). Int J Oncol, 42, 1133-8. https://doi.org/10.3892/ijo.2013.1829
  24. Tanaka Y, Inoue T, Horie H (2013). International pediatric liver cancer pathological classification: current trend. Int J Clin Oncol, 18, 946-54. https://doi.org/10.1007/s10147-013-0624-8
  25. Terada Y, Matsumoto S, Bando K, Tajiri T (2009). Comprehensive allelotyping of hepatoblastoma. Hepatogastroenterology, 56, 199-204.
  26. Teramoto T, Satonaka K, Kitazawa S, et al (1994). p53 gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis. Cancer Res, 54, 231-5.
  27. Thongbai C, Sa-nguanmoo P, Kranokpiruk P, et al (2013). Hepatitis B virus genetic variation and TP53 R249S mutation in patients with hepatocellular carcinoma in Thailand. Asian Pac J Cancer Prev, 14, 3555-9. https://doi.org/10.7314/APJCP.2013.14.6.3555
  28. Tomlinson GE, Kappler R (2012). Genetics and epigenetics of hepatoblastoma. Pediatr Blood Cancer, 59, 785-92. https://doi.org/10.1002/pbc.24213
  29. Weinberg RA (1995). The retinoblastoma protein and cell cycle control. Cell, 81, 323-30. https://doi.org/10.1016/0092-8674(95)90385-2

피인용 문헌

  1. Association of a p53 Codon 72 Gene Polymorphism with Environmental Factors and Risk of Lung Cancer: a Case Control Study in Mizoram and Manipur, a High Incidence Region in North East India vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10653
  2. High Quality Tissue Miniarray Technique Using a Conventional TV/Radio Telescopic Antenna vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.1129
  3. Effects of Epothilone A in Combination with the Antidiabetic Drugs Metformin and Sitagliptin in HepG2 Human Hepatocellular Cancer Cells: Role of Transcriptional Factors NF-κB and p53 vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.993