The role of p53 as a surrogate marker for chemotherapeutical responsiveness in ovarian cancer.
BACKGROUND
In advanced ovarian cancers (OCs), p53 mutations are frequently observed. The objective of this study was to explore the value of the p53 mutational status, using four different techniques, in advanced OC patients as a predictive marker for responsiveness to platinum-based chemotherapy.


METHODS
One hundred and four, mostly serous papillary OC specimens were analyzed, of which all received a platinum containing chemotherapy after optimal cyto-reductive surgery. To verify the p53 mutational status, immunohistochemical staining with monoclonal antibodies, functional yeast assay (FASAY), single-strand conformation polymorphism analysis (SSCP) and genomic sequencing was performed in parallel.


RESULTS
Out of ten OC patients [2 low malignant potential (LMP)/8 G1] only two had a mutant p53, whereas eight showed a wild-type p53. 40 out of 63 (G2/3) patients with G2/3 OC showed mutant p53 and 23 patients showed a wild-type pattern. p53 status was significantly different between these two groups (LMP/G1 vs. G2/3) (P = 0.015). A progressive disease after chemotherapy completion was noted in 35.6% of the patients (26 out of 73); in 69.2%, a mutated p53 and in 30.8%, a wild-type p53 was found. Nine (12.3%) patients showed a complete response at the end of the first-line chemotherapy. Out of these nine patients five had a mutated and four a wild-type p53. A partial response was observed in nine (12.3%) patients of whom four had a mutated p53. With respect to response to first-line chemotherapy (six cycles of platinum containing regimen), the p53 status was not predictive; no statistical significance regarding the p53 mutational status was observed when the two extreme groups PD versus PR/CR were compared (P > 0.05).


CONCLUSIONS
In this study, the p53 mutational status was not predictive for responsiveness to platinum-based chemotherapy; but p53 was significantly more frequently mutated in poorly differentiated OCs.
Bauerschlag
Dirk O
DO
Department of Gynecology and Obstetrics University Hospital, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. dbauerschlag@ukaachen.de
Schem
Christian
C
Weigel
Marion T
MT
Von Kaisenberg
Constantin
C
Strauss
Alexander
A
Bauknecht
Thomas
T
Maass
Nicolai
N
Meinhold-Heerlein
Ivo
I
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D018807:Polymorphism, Single-Stranded Conformational; D013514:Surgical Procedures, Operative / Q000379:methods; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53