Liu F S, Ho E S, Chen J T, Shih R T, Yang C H, Shih A
Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taiwan, Republic of China.
Cancer. 1995 Jul 15;76(2):291-5. doi: 10.1002/1097-0142(19950715)76:2<291::aid-cncr2820760220>3.0.co;2-2.
The p53 tumor suppressor gene has been well studied in epithelial ovarian cancers. However, little is known of the expression of this gene in ovarian germ cell tumors. The authors attempted to investigate whether p53 alterations occurred in this group of tumors.
Twenty-two patients with malignant ovarian germ cell tumors were included in this study. Immunohistochemical staining for p53 was performed on paraffin embedded tissue of each case. Single-strand conformation polymorphism analysis of exons 4-9 of the p53 gene was performed on 9 of the 22 tumors where genomic DNAs were obtained from the frozen tissue samples. Three tumors that revealed focal p53 positivity by immunostaining were studied further with direct DNA sequencing.
Overexpression of p53 was not observed in all of the 22 ovarian germ cell tumors; only 3 were found to have nuclear staining in a small fraction of the malignant cells (< 5% in 1 immature teratoma, 5-10% in 2 yolk-sac tumors). Among the nine frozen tumors subjected to single-strand conformation polymorphism analysis, none revealed p53 mutation in exons 4-9. There was no p53 mutation detected by DNA sequencing of the three tumors with focal immunoreactivity.
Alterations of the p53 tumor suppressor gene may not be associated with the pathogenesis of ovarian germ cell tumors. Instead, genetic changes such as inactivation of other tumor suppressor genes and/or activation of some protooncogenes need to be studied to determine the genetic mechanisms of the tumor development.
p53肿瘤抑制基因在上皮性卵巢癌中已得到充分研究。然而,对于该基因在卵巢生殖细胞肿瘤中的表达情况却知之甚少。作者试图研究这组肿瘤中是否发生了p53改变。
本研究纳入了22例恶性卵巢生殖细胞肿瘤患者。对每例患者的石蜡包埋组织进行p53免疫组织化学染色。对22例肿瘤中的9例进行了p53基因第4至9外显子的单链构象多态性分析,这些肿瘤的基因组DNA取自冷冻组织样本。对3例免疫染色显示p53局灶阳性的肿瘤进一步进行直接DNA测序。
在所有22例卵巢生殖细胞肿瘤中均未观察到p53过表达;仅3例在一小部分恶性细胞中发现有核染色(1例未成熟畸胎瘤中<5%,2例卵黄囊瘤中为5 - 10%)。在接受单链构象多态性分析的9例冷冻肿瘤中,未发现第4至9外显子有p53突变。对3例有局灶免疫反应性的肿瘤进行DNA测序,未检测到p53突变。
p53肿瘤抑制基因的改变可能与卵巢生殖细胞肿瘤的发病机制无关。相反,需要研究其他肿瘤抑制基因失活和/或某些原癌基因激活等基因变化,以确定肿瘤发生发展的遗传机制。