Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer.
OBJECTIVE
p27 protein is regarded as a valuable prognostic biomarker in cancer with a potential use as a molecular target. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of p27 in ovarian cancer using a novel method of compartmentalized in situ protein analysis.


METHODS
A tissue array composed of 150 advanced stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of p27 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis [automated quantitative analysis (AQUA)].


RESULTS
The mean follow-up time of the patients was 34.3 months. Patients with low Fédération Internationale des Gynaecologistes et Obstetristes stage were more likely to have low nuclear p27 expression (P = 0.008). Low nuclear p27 expression was associated with improved 3-year overall survival (66% versus 20%, P = 0.0047) and disease-free survival (27% versus 12%, P = 0.022). In multivariable analysis, adjusting for well-characterized prognostic variables, low nuclear p27 expression level was the most significant prognostic factor for both disease-free and overall survival.


CONCLUSIONS
Our results indicate that quantitative assessment of nuclear p27 expression level by automated in situ quantitative analysis is a strong predictor for outcome in ovarian cancer.
Psyrri
Amanda
A
Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. diamando.psyrri@yale.edu
Bamias
Aris
A
Yu
Ziwei
Z
Weinberger
Paul M
PM
Kassar
Mohamad
M
Markakis
Sophia
S
Kowalski
Diane
D
Efstathiou
Eleni
E
Camp
Robert L
RL
Rimm
David L
DL
Dimopoulos
Meletios A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D015331:Cohort Studies; D003131:Combined Modality Therapy; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D013347:Subcellular Fractions; D015996:Survival Rate; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27