Abstract
Objective: To investigate expression and significance of PTEN gene in primary hepatocellular carcinoma (HCC). Methods: Immunohistochemical peroxidase‐conjugated streptavidin (SP) method was used to detect expression of PTEN gene in 120 cases of primary HCC and its adjacent tissue 10 cases of normal liver tissue. The relationship between expression of tumor suppressor gene of PTEN and the percentage of lymph node metastasis of HCC was analyzed. Results: It was shown that PTEN gene was expressed in all 10 cases of normal liver tissues and paracancerous liver tissues. The staining was localized mainly in cytoplasm. Expression of PTEN in 120 cases of HCC were as follows: 12.5% were negative, 17.5% were weak positive, and 70% were strong positive. At time of diagnosis, 33/120 (27.5%) presented lymph node metastasis. Lymph node metastases were present in 80% (12 out of 15) PTEN negative HCC, 57.14% (12 out of 21) PTEN weak positive HCC and only 10.71% (9 out of 84) PTEN intense positive HCC, (P<0.05). Therefore, PTEN tumor suppresor gene malfunction seems to be involed in mtastasing capacity of HCC. Conclusion: This study suggests that PTEN gene was deleted or weakly expressed in primary hepatocellar carcinoma, which is probably related to its tumorigenesis.
Keywords: tumor suppressor gene PTEN, hepatocellular carcinoma, expression, metastasis
References
- 1. Li J., Yen C., Liaw D., et al., PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, and prostate cancer, Science, 275: 1943–1947, 1997. [DOI] [PubMed] [Google Scholar]
- 2. Li D.‐M., Sun H., TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine prosphatase regulated by transforiming growth factor B, Cancer Res., 57: 2124–2129, 1997. [PubMed] [Google Scholar]
- 3. Steck P.A., Pershouse M.A., Jasser S.A., et al., Identification of a candidate tumor suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers, Nat. Genet., 15: 356–362, 1997. [DOI] [PubMed] [Google Scholar]
- 4. Kondo Ki, Yao M., Kobayashi K., et al., PTEN/MMAC1/TEP1 mutations in human primary real‐cell carcinomas and renal carcinoma cell lines, Int. J. Cancer, 91: 219–224, 2001. [DOI] [PubMed] [Google Scholar]
- 5. Cantley L.C., Neel B.G., New insights into tumor suppession PTEN suppress tumor formation by restaining the phospho‐inositide 3‐kinaes/Akt pathway, Proc. Natl. Sci. USA, 96:4240–4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Bose S., Wang S.I., Terry M.B., Parsons R. et al., Allelic loss of chromosome 10q23 is associated with tumor progression is breast carcinomas, Oncogene, 17: 123–1277, 1998. [DOI] [PubMed] [Google Scholar]
- 7. Stambolic V., Suuki A., Pompa J.L., et al., Negative regulation of PKB/Akt dependent cell survival by the tumor suppressor PTEN, Cell, 95: 29–39, 1998. [DOI] [PubMed] [Google Scholar]
- 8. Vazquez F., Seller W.R., The PTEN tumour suppressor protein:an antagonist of phosphoinositide 3‐kinase signaling, Biochem. Biophys. Acta, 1470:M21–M25, 2000. [DOI] [PubMed] [Google Scholar]
- 9. Feilotter H.E., Coulon V., McVeigh J.L., et al., Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma, Br. J. Cancer, 79: 1201–1205, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Whang Y.E., Wu X., Suzuki H., et al., Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression, Proc. Natl. Acad. Sci. USA, 95: 5246–5250, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Tamura M., Gu J.G., Matsumoto K., Inhibition of cell migration, spreading and focal adhesion by tumor suppressor PTEN, Science, 280:1614–1617, 1998. [DOI] [PubMed] [Google Scholar]
- 12. David O., Akt and PTEN: new diagnostic markers of nonsmall cell lung cancer?, J. Cell Mol. Med., 5: 430–433, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Popescu N.C., Comprehensive genetic analysis of cancer cells, J. Cell Mol. Med., 4: 151–163, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
