title: Prognostic significance of the mitochondrial scoring system in ovarian cancer.
abstract: We report a mitochondrial (MT) scoring system related to response to platinum treatment in ovarian cancer (OC). Ultra-thin sections of surgical specimens of primary tumors prepared from 41 OC patients were examined by electron microscopy. The ovarian carcinoma cell line 2008 and its platinum-resistant variant C13 were used as controls. Seven independent MT features, including MT diameter, pattern of cresta structure, electron density, MT distribution, pattern of distribution, ovoid ratio and MT architecture, were examined. Each of the seven parameters was assigned a point score of 0-2 and was summed up with a total score of 14. Clinical response and in vitro sensitivity to platinum, taxane, irinotecan and doxorubicin were evaluated. Clinical information was available for 37 of the 41 cases. Twenty-four cases were stage III and, histologically, 16 serous, 6 endometrioid and 6 clear cell carcinoma were included. All of the patients underwent surgery followed by 6 cycles of taxane and platinum chemotherapy. Fifteen patients exhibited a response, while 22 were resistant to treatment. The total MT score was 5.13±1.13 (mean ± SE) in the 15 responsive cases and 11.41±0.43 in the 22 resistant cases (P<0.001). Receptor operative characteristic (ROC) analysis revealed that the resistant total 'cut-off' score was ≥10 points (P<0.05; AUC=0.86) with 95.5% sensitivity and 80.0% specificity. The MT scoring system correlated well with response to drugs, with the exception of doxorubicin. The progression-free survival (PFS) curves showed an absolute difference in the 6-month PFS of 10% (83 vs. 73%) and in the 12-month PFS of 21% (80 vs. 59%), in favor of patients with low MT scores. This MT scoring system correlates very closely with clinical response as well as cellular sensitivity to chemotherapy, resulting in an association with PFS.
authors.affiliation: Departments of Obstetrics/Gynecology.
authors.forename: Ryuma
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hamada
authors.forename: Takako
authors.initials: T
authors.lastname: Kiyokawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tachibana
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa