Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer.
Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer.
复制标题
DOI：
--
复制
发表时间：
1999-08
期刊：
影响因子：
11.2
通讯作者：
V. Masciullo;A. Sgambato;C. Pacilio;B. Pucci;G. Ferrandina;J. Palazzo;A. Carbone;A. Cittadini;S. Mancuso;G. Scambia;A. Giordano
中科院分区：
文献类型：
--
作者：
V. Masciullo;A. Sgambato;C. Pacilio;B. Pucci;G. Ferrandina;J. Palazzo;A. Carbone;A. Cittadini;S. Mancuso;G. Scambia;A. Giordano
p27 Kip 1是细胞周期蛋白依赖性激酶抑制剂Cip 1/Kip 1家族的成员，是一个潜在的肿瘤抑制基因。低水平的p27与多种肿瘤的不良预后相关，包括乳腺癌、结肠癌、前列腺癌和肺癌。在本研究中，p27蛋白的表达进行了研究，通过免疫组化和蛋白质印迹分析在一系列的82上皮性卵巢肿瘤[16分类为低恶性潜能（LMP）和66分类为原发性卵巢腺癌]。免疫组化分析显示，原发性卵巢腺癌（33%），相对于LMP肿瘤（6%; P = 0.0009）的p27表达频繁的损失。除核染色外，82例中有45例（55%）的p27细胞质定位。在肿瘤的代表性子集中，p27水平与CDK 2激酶活性负相关。当评估患者的临床结果与p27状态的关系时，我们观察到p27染色的存在与较长的进展时间之间存在显著相关性（对数秩检验P = 0.032）。这些数据表明，与LMP肿瘤相比，p27的丢失在卵巢癌中是一个常见的事件，这表明这些肿瘤类型可能具有不同的发病机制。p27水平也可能是预测原发性卵巢癌复发的一个有用的预后指标。
p27Kip1 is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of tumors, including breast, colon, prostate, and lung carcinomas. In the present study, p27 protein expression was investigated by immunohistochemistry and Western blot analysis in a series of 82 epithelial ovarian tumors [16 classified as low malignant potential (LMP) and 66 classified as primary ovarian adenocarcinomas]. Immunohistochemical analysis revealed frequent loss of p27 expression in primary ovarian adenocarcinomas (33%), with respect to LMP tumors (6%; P = 0.0009). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 45 (55%) of 82 cases. p27 levels inversely correlated with cdk2 kinase activity in a representative subset of tumors. When the clinical outcome of the patients was evaluated in relationship to p27 status, we observed a significant correlation between presence of p27 staining and a longer time to progression (P = 0.032 by log-rank test). These data indicate that loss of p27 is a frequent event in ovarian carcinomas as compared with LMP tumors, suggesting that these tumor types may have different pathogenesis. p27 levels may also represent a useful prognostic marker for predicting disease recurrence in primary ovarian carcinomas.