Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865).
OBJECTIVE
The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865.


METHODS
Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC).


RESULTS
Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors.


CONCLUSIONS
P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.
Green
J A
JA
Division of Surgery and Oncology, University of Liverpool, United Kingdom, and Department of Gynecologic Oncology, Free University Hospital, Amsterdam, The Netherlands. J.A.Green@liverpool.ac.uk
Berns
E M J J
EM
Coens
C
C
van Luijk
I
I
Thompson-Hehir
J
J
van Diest
P
P
Verheijen
R H M
RH
van de Vijver
M
M
van Dam
P
P
Kenter
G G
GG
Tjalma
W
W
Ewing
P C
PC
Teodorovic
I
I
Vergote
I
I
van der Burg
M E L
ME
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003520:Cyclophosphamide; D002945:Cisplatin