Abdel-Fattah G, Yoffe B, Krishnan B, Khaoustov V, Itani K
DeBakey Department of Surgery, Departments of Medicine and Pathology, Houston VA Medical Center, Houston, Texas 77030, USA.
J Gastrointest Surg. 2000 Jan-Feb;4(1):109-14. doi: 10.1016/s1091-255x(00)80041-4.
The murine double minutes 2 (MDM2) oncoprotein inhibits p53-mediated tumor suppression. MDM2 has been shown to be overexpressed in sarcomas and more recently was implicated in the pathogenesis of carcinomas. The purpose of this study was to determine the expression pattern of MDM2 in adenomas and colorectal adenocarcinomas and decide whether there is a correlation between MDM2 and p53 protein status. Paraffin-embedded tissues from 52 colorectal cancer (CRC) specimens and their adjacent normal tissue (N-CRC) were studied. In addition, 56 sporadic adenomas were investigated for the immunohistochemical expression of MDM2 and p53 proteins. Immunoreactivity of p53 indicating p53 gene mutation (p53+) was significantly higher in CRC (44%) compared to adenomas (23.2%) (P <0.01). None of the N-CRC specimens expressed the immunoreactive p53 protein. MDM2 overexpression (MDM2+) was similar in adenomas (30.3%) and CRC (25%), but only 2 (3.8%) of 52 N-CRC specimens showed overexpression of MDM2. In most cases MDM2 expression was associated with negative p53 expression (wild-type p53) in both adenomas (r = 0.59, P <0.001) and CRC (r = 0.69, P <0. 0001). No correlation was found between MDM2, p53 expression, and either the histologic grade, nodal stage or morphology of the tumors. There is greater p53 mutation in CRC compared to adenomas and N-CRC. The data indicate that MDM2 is overexpressed in CRC and is significantly associated with wild-type p53 compared to N-CRC specimens from the same patient. The MDM2 expression pattern is similar in adenomas and CRC, which may suggest that MDM2 overexpression is an early event in the progression of CRC.
小鼠双微体2（MDM2）癌蛋白可抑制p53介导的肿瘤抑制作用。已有研究表明，MDM2在肉瘤中过表达，最近又发现其与癌的发病机制有关。本研究的目的是确定MDM2在腺瘤和结直肠癌中的表达模式，并判断MDM2与p53蛋白状态之间是否存在相关性。对52例结直肠癌（CRC）标本及其相邻正常组织（N-CRC）的石蜡包埋组织进行了研究。此外，还对56例散发性腺瘤进行了MDM2和p53蛋白的免疫组化表达研究。与腺瘤（23.2%）相比，CRC中显示p53基因突变（p53+）的p53免疫反应性显著更高（44%）（P<0.01）。所有N-CRC标本均未表达免疫反应性p53蛋白。腺瘤（30.3%）和CRC（25%）中MDM2过表达（MDM2+）情况相似，但52例N-CRC标本中只有2例（3.8%）显示MDM2过表达。在大多数情况下，腺瘤（r = 0.59，P<0.001）和CRC（r = 0.69，P<0.0001）中MDM2表达均与p53阴性表达（野生型p53）相关。未发现MDM2、p53表达与肿瘤的组织学分级、淋巴结分期或形态之间存在相关性。与腺瘤和N-CRC相比，CRC中的p53突变更多。数据表明，与同一患者的N-CRC标本相比，MDM2在CRC中过表达，且与野生型p53显著相关。腺瘤和CRC中的MDM2表达模式相似，这可能表明MDM2过表达是CRC进展过程中的早期事件。
