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J Cancer Res Clin Oncol (2006) 132:811816 DOI 10.1007/s00432-006-0130-8
ORIGINAL PAPER
[afii9797]Np63 protein expression in uterine cervical and endometrial cancers
Zhenhua Lin Mingzhu Liu Zhuhu Li Changheon Kim Eungseok Lee Insun Kim
Received: 9 December 2005 / Accepted: 29 May 2006 / Published online: 28 June 2006 Springer-Verlag 2006
Abstract
Purpose To investigate the signiWcance of p63 expression in uterine cervical and endometrial cancers. Materials and methods [afii9797]Np63 protein expression was studied in a variety of 127 cases of uterine cervical lesions (20 non-neoplastic cervices, 43 cervical intraepithelial neoplasia [CIN], 54 squamous cell carcinomas (SCCs), 40 adenocarcinomas, and 13 other histologic types) and 30 endometrioid type of endome-trial adenocarcinomas by using immunohistochemistry. One SCC cell line (ME-180) and one adenocarcinoma cell line (HeLa) were also included.
Results In uterine cervix, the expression of [afii9797]Np63 was increased with progression of CIN, and positive in all SCCs, transitional cell carcinomas, and adenoid basal carcinoma, but negative in all adenocarcinomas. Adenosquamous cell carcinoma and mixed neuroendocrine and squamous cell carcinoma were positive in squa-
mous component, but not in adenocarcinoma and neuroendocrine carcinoma components. ME-180 cell line was positive, whereas HeLa cell line was negative. Endometrioid type of endometrial adenocarcinomas showed a positive staining in glandular (26.7%) and squamous component.Conclusions Immunohistochemical staining for [afii9797]Np63 is a powerful marker for squamous diVerentiation and useful in exclusion of glandular and neuroendocrine diVerentiation in uterine cervical cancers, but not always in endometrial cancers.
Keywords [afii9797]Np63 Uterine cervical cancer Endometrial cancer
Introduction
p63, the family of p53 tumor suppressor gene, located on 3q2729 and contains 15 exons (Kaelin 1999; Little and Jochemsen 2002; Trink et al. 1998). It has a single promoter with three conserved domains (transactivation domain, DNA binding domain, oligomerization domain), and has two diVerent types of protein; those containing the TA domain (TAp63) and those lacking the TA domain ([afii9797]Np63) (Benard et al 2003; Little and Jochemsen 2002; Yang et al. 1998). The gene undergoes complex alternative splicing at the carboxy-terminus, giving rise to three isoforms ([afii9825], [afii9826], [afii9828]) (Little and Jochemsen 2002; Westfall and Petenpol 2004).
Unlike p53, the p63 gene is rarely mutated in human primary tumors and cell lines. However, overexpression of p63 protein has been reported in a variety of human neoplasms, including cervical cancer,...