Expression and subcellular localization of the cyclin-dependent kinase inhibitor p27(Kip1) in epithelial ovarian cancer.
OBJECTIVE
To determine if p27(Kip1) expression was altered in epithelial ovarian cancers as compared to normal ovarian surface epithelial (NOSE) cells and to determine if subcellular localization of p27(Kip1) was an important feature.


METHODS
Thirteen tumor samples (1 Stage IC [early] and 12 Stage III/IV [advanced]) from patients with epithelial ovarian cancer and five NOSE samples were evaluated. Samples were surgically dissected to obtain an enriched population (90%) of cancer cells. The level of p27(Kip1) protein expression was determined by Western blot analysis. Actin was used as a loading control, and results were quantified by scanning densitometry using the ratio of the p27(Kip1) signal to the actin signal for comparison. To evaluate the subcellular localization of p27(Kip1), immunocytochemical staining was performed. Clinical pathological parameters were correlated to nuclear p27(Kip1) staining to establish if any association existed.


RESULTS
When comparing the expression of p27(Kip1) between NOSE and ovarian cancer samples, only 2 of 13 ovarian cancer samples had altered p27(Kip1) expression. No correlation was found between the expression level of p27(Kip1) on Western blot and clinical pathological correlates. While no correlation between expression level of p27(Kip1) and subcellular localization was found, decreased nuclear staining (1+) was associated with shorter survivals using the log-rank test (P < 0.001). More importantly, in all tumor samples examined under the microscope, no nuclear p27(Kip1) staining was noted in cells that were undergoing mitosis.


CONCLUSIONS
p27(Kip1) protein degradation may not be modified in ovarian cancer cells undergoing mitosis. Altered expression of p27(Kip1) is not an overwhelming feature in certain epithelial ovarian cancers. Decreased nuclear staining of p27(Kip1) is associated with poor survival in some epithelial ovarian cancers.
Hurteau
J A
JA
Department of Obstetrics and Gynecology, Indiana University Cancer Center, Indianapolis, Indiana 46202, USA. jhurteau@iupui.edu
Allison
B M
BM
Brutkiewicz
S A
SA
Goebl
M G
MG
Heilman
D K
DK
Bigsby
R M
RM
Harrington
M A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000378:metabolism*
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases