HE4 expression in plasma correlates with surgical outcome and overall survival in patients with first ovarian cancer relapse.
BACKGROUND
Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).


METHODS
Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher's exact test, Kendall's tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan-Meier method.


RESULTS
At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601-0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68-75.25; and p = 0.044, HR 3.33, 95 % CI 1.03-10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22-42.19 and p = 0.036, OR 10.18, 95 % CI 1.16-88.69, respectively).


CONCLUSIONS
HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.
Gynecological Department, Charité Medizinische Universität Berlin, Campus Virchow Klinikum, Berlin, Germany, elena.braicu@charite.de.
Elena Ioana
EI
Braicu
Radoslav
R
Chekerov
Rolf
R
Richter
Carmen
C
Pop
Mani
M
Nassir
Hanna
H
Loefgren
Florin
F
Stamatian
Mustafa Zelal
MZ
Muallem
Christina
C
Hall
Christina
C
Fotopoulou
Jalid
J
Sehouli
Klaus
K
Pietzner
D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000401:mortality* / Q000601:surgery; D000328:Adult; D000368:Aged; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000401:mortality* / Q000601:surgery; D016889:Endometrial Neoplasms / Q000097:blood / Q000401:mortality* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000097:blood / Q000401:mortality* / Q000601:surgery; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D015996:Survival Rate; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human