Werness B A, Jobe J S, DiCioccio R A, Piver M S
Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York 14623-0001, USA.
Int J Gynecol Pathol. 1997 Apr;16(2):149-55. doi: 10.1097/00004347-199704000-00011.
Mutations of the p53 gene are the most common genetic alteration in malignant human tumors, including ovarian carcinomas of surface epithelial origin. A cyclin-dependent kinase inhibitor, p21waf1/cip1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in ovarian tumors, none have correlated p53 expression with that of its downstream effector, p21waf1/cip1. We studied p53 and p21waf1/cip1 expression by immunohistochemistry in 44 ovarian carcinomas of different histologic types and correlated these findings with each other and with proliferation as measured by expression of the Ki-67 nuclear antigen. Fifty percent of tumors expressed p53, whereas 34% expressed p21waf1/cip1. Clear cell carcinomas expressed p21waf1/cip1 significantly more often than other histologic types, and tumors with squamous differentiation showed higher p21waf1/cip1 expression in these areas. There was no correlation of p21waf1/cip1 expression with p53 expression, p53 mutation, or Ki-67 expression. p21waf1/cip1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.
p53基因的突变是人类恶性肿瘤中最常见的基因改变,包括表面上皮来源的卵巢癌。细胞周期蛋白依赖性激酶抑制剂p21waf1/cip1被认为是p53诱导细胞周期停滞的重要介质。尽管众多研究报道了卵巢肿瘤中的p53表达和突变,但尚无研究将p53表达与其下游效应物p21waf1/cip1的表达相关联。我们通过免疫组织化学研究了44例不同组织学类型卵巢癌中的p53和p21waf1/cip1表达,并将这些结果相互关联,同时与通过Ki-67核抗原表达测量的增殖情况相关联。50%的肿瘤表达p53,而34%表达p21waf1/cip1。透明细胞癌比其他组织学类型更频繁地表达p21waf1/cip1,并且具有鳞状分化的肿瘤在这些区域显示出更高的p21waf1/cip1表达。p21waf1/cip1表达与p53表达、p53突变或Ki-67表达均无相关性。在这些肿瘤中,p21waf1/cip1似乎独立于p53被诱导,并且可能与分化而非增殖相关。