Clinical significance of p27 and Skp2 protein expression in uterine cervical neoplasm

被引:17
作者
Kim, Jung Yeon
Lim, Sung-Jig
Kim, Hyun-Jung
Shin, Eunah
Park, Kyeongmee
Lee, Chul-Min
机构
[1] Inje Univ, Sanggye Paik Hosp, Dept Pathol, Seoul, South Korea
[2] Inje Univ, Sanggye Paik Hosp, Dept Obstet & Gynecol, Seoul, South Korea
关键词
p27; Skp2; uterine cervix; neoplasm;
D O I
10.1097/pgp.0b013e31802c4be5
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
The loss of p27 indicates a poor prognosis in various solid tumors, and a decrease in p27 level is the result of increased degradation by Skp2. We evaluated the relationship of p27 and Skp2 protein expression to various clinicopathologic factors in 332 cases of untreated uterine cervical neoplasm using tissue microarray method. After immunohistochemical staining, 313 and 300 tumor samples were retrieved for interpretation for p27 and Skp2, respectively. High p27 protein expression (nuclear staining in more than 30% of the tumor cells) was seen in 39.9% (125/313 cases), including 32 cervical intraepithelial neoplasia (CIN) 111 (55.2%), 58 microinvasive squamous cell carcinoma (SCC) (56.9%), 21 invasive SCC (17.1%), 11 adenocarcinoma (55.0%) and 3 cases of other tumors (30.0%). High Skp2 protein expression was noted in 28.3% (85/300 cases), including 14 cervical intraepithelial neoplasia 111 (25.0%), 18 microinvasive SCC (18.75%), 45 invasive SCC (37.8%), 6 adenocarcinoma (30.0%), and 2 cases of other tumors (22.2%). Low p27 protein expression was correlated with large tumor size (P < 0.005), depth of invasion in squamous lesion (P < 0.0005), high stage (P < 0.0005), and poor survival (P < 0.005). High Skp2 protein expression was correlated with large tumor size (P < 0.05), depth of invasion in squamous lesion (P < 0.05), and high stage (P < 0.005), but not with patient survival. There was no significant correlation between p27 and Skp2 protein expression. Only tumor stage had prognostic significance in the multivariate analysis (P = 0.041). Patients with low p27 protein expression had worse prognosis, indicating that p27 may participate in the progression of cervical squamous cell lesions.
引用
收藏
页码:242 / 247
页数:6
相关论文
共 35 条
[1]  
Anayama T, 1998, INT J CANCER, V79, P439, DOI 10.1002/(SICI)1097-0215(19980821)79:4<439::AID-IJC22>3.0.CO
[2]  
2-Z
[3]   Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27Kip1 in prostate cancer [J].
Ben-Izhak, O ;
Lahav-Baratz, S ;
Meretyk, S ;
Ben-Eliezer, S ;
Sabo, E ;
Dirnfeld, M ;
Cohen, S ;
Ciechanover, A .
JOURNAL OF UROLOGY, 2003, 170 (01) :241-245
[4]   p27Kip1 modulates cell migration through the regulation of RhoA activation [J].
Besson, A ;
Gurian-West, M ;
Schmidt, A ;
Hall, A ;
Roberts, JM .
GENES & DEVELOPMENT, 2004, 18 (08) :862-876
[5]   Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase [J].
Bornstein, G ;
Bloom, J ;
Sitry-Shevah, D ;
Nakayama, K ;
Pagano, M ;
Hershko, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (28) :25752-25757
[6]   SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27 [J].
Carrano, AC ;
Eytan, E ;
Hershko, A ;
Pagano, M .
NATURE CELL BIOLOGY, 1999, 1 (04) :193-199
[7]  
Cheng JD, 1999, CLIN CANCER RES, V5, P1057
[8]   Alteration of cell cycle in cervical tumor associated with human papillomavirus - Cyclin-dependent kinase inhibitors [J].
Cho, NH ;
Kim, YT ;
Kim, JW .
YONSEI MEDICAL JOURNAL, 2002, 43 (06) :722-728
[9]   Cell cycle aberrations in the pathogenesis of squamous cell carcinoma of the uterine cervix [J].
Clarke, B ;
Chetty, R .
GYNECOLOGIC ONCOLOGY, 2001, 82 (02) :238-246
[10]   Overexpression of Skp2 in carcinoma of the cervix does not correlate inversely with p27 expression [J].
Dowen, SE ;
Scott, A ;
Mukherjee, G ;
Stanley, MA .
INTERNATIONAL JOURNAL OF CANCER, 2003, 105 (03) :326-330