Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer.
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.
Masciullo
V
V
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Sgambato
A
A
Pacilio
C
C
Pucci
B
B
Ferrandina
G
G
Palazzo
J
J
Carbone
A
A
Cittadini
A
A
Mancuso
S
S
Scambia
G
G
Giordano
A
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015993:Life Tables; D019656:Loss of Heterozygosity; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases