P21WAF1/Cip1 gene expression in primary human hepatocellular carcinoma and its relationship with P53 gene mutation
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P21WAF1/Cip1, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the P53-specfic pathway of growth control. Increased expression of P21WAF1/Cip1 has been found to reflect the status of the P53 tumor-suppressor pathway. We investigated the expression of P21WAF1/Cip1 in a relatively small, but well-characterized group consisting of 28 hepatocellular carcinomas. The samples were previously studied for P53 gene mutation. P21WAF1/Cip1 expression were identified byin situ hybridization and immunohistochemistry. Positive ISH for P21WAF1/Cip1 transcripts was found in 18 of 28 cases (64. 3 %). All positive cases by ISH showed detectable P21WAF1/Cip1 protein reactivity by IHC. No relationship was found between p21WAF1/Cip1 staining and P53 mutational status. No associations were seen with tumor metastasis, size and tumor grade, except for tumor differentiation status which showed higher frequency of P21WAF1/Cip1 expression in moderate-well differentiated HCCs than poorly differentiated tumors (P< 0. 05). It is concluded that expression of P21WAF1/Cip1 is common in HCCs, but does not correlate with P53 mutational status or pathological parameters investigated except for tumor differentiation. Also, there may be other factors beside P53 that regulate P21WAF1/Cip1 gene expression in HCCs.
Key wordshepatocellular carcinoma P53 P21WAF1/Cip1
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- 3.Michieli P, Chedid M, Lin Det al. Induction of WAF1/cip1 by a P53 independent pathway. Can Res, 1994, 54:3391Google Scholar
- 4.Slebos R J C, Baas I O, Clement Met al. Clinical and pathological association with P53 tumour suppressor gene mutation and expression of P21WAF1/Cip1 in colorectal carcinoma. Br J Can, 1996, 74:165Google Scholar
- 5.El-Deiry W S, Tokino T, Waldamwn Tet al. Topological control of P21WAF1/Cip1 expression in normal and neoplastic tissues. Can Res, 1995, 55:2910Google Scholar
- 6.Marchetti A, Buttitta F, Pellegrini Set al. Absence of somatic mutation in the coding region of the Waf1/Cip1 gene in human breast, lung and ovarian carcinoma: a polymorphism at codon 31. Int J Oncol, 1995, 6:187Google Scholar
- 7.Marchetti A, Doglion C, Barbareschi Met al. P21 mRNA and protein expression in non-small cell lung carcinoma: evidence of P53 independent expression and association with tumoral differentiation. Oncogene, 1996, 11:200Google Scholar
- 8.Doglioni C, Pelosio P, Laurino Let al. P21WAF1/Cip1 expression in normal mucosa, adenomas and adenocarcinomas of the colon: its relationship with differentiation. J Pathol, 1996, 56:56Google Scholar
- 10.Steinman R A, Hoffman B, Iro Aet al. Induction of P21WAF1/Cip1 during differentiation. Oncogene, 1994, 9:3–389Google Scholar
- 13.Wan M, Cofer K F, Dubeau Let al. WAF1/ Cip1 structural abnormalities do not contributes to cell cycle deregulation in ovarian cancer. Br J Can, 1996, 73:1–398Google Scholar