Summary
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.
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References
El-deiry W S, Tokino T, Velculescu V Eet al. WAF1, a potential mediator of P53 tumor suppression. Cell, 1993, 75:817
Noda A, Ning Y, Venable S Fet al. Clonation of senescent cell derived inhibitor of DNA synthesis using an expression screen. Exp Cell Res, 1994, 211:90
Michieli P, Chedid M, Lin Det al. Induction of WAF1/cip1 by a P53 independent pathway. Can Res, 1994, 54:3391
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, 74:165
El-Deiry W S, Tokino T, Waldamwn Tet al. Topological control of P21WAF1/Cip1 expression in normal and neoplastic tissues. Can Res, 1995, 55:2910
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, 6:187
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, 11:200
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, 56:56
Florenes P, Malandsmo G M, Forus Aet al. Mdm2 gene amplification and transcript levels in human sarcomas: relationship to TP53 gene status. J Natl Can Inst, 1994, 86:1297
Steinman R A, Hoffman B, Iro Aet al. Induction of P21WAF1/Cip1 during differentiation. Oncogene, 1994, 9:3–389
Halevy O, Novitch B G, Spicer D Bet al. Correlation of terminal cell cycle arrest of skeletal muscle with induction of P21 by MyoD. Science, 1995, 267:1–018
Li X Y, Puig P L, Salmon R Jet al. Polymorphisms and probable lack of mutation in the WAF1/Cip1 gene in colorectal cancer. Oncogene, 1995, 10:599
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, 73:1–398
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Baohua, S., Zhongbi, W., Youbing, R. et al. P21WAF1/Cip1 gene expression in primary human hepatocellular carcinoma and its relationship with P53 gene mutation. Journal of Tongji Medical University 19, 1–5 (1999). https://doi.org/10.1007/BF02895583
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DOI: https://doi.org/10.1007/BF02895583