Matsumoto Ryuma, Isonishi Seiji, Ochiai Kazuhiko, Hamada Tomomi, Kiyokawa Takako, Tachibana Toshiaki, Ishikawa Hiroshi
Departments of Obstetrics/Gynecology.
Exp Ther Med. 2010 Sep;1(5):783-788. doi: 10.3892/etm.2010.118. Epub 2010 Jul 20.
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.
我们报告了一种与卵巢癌（OC）铂类治疗反应相关的线粒体（MT）评分系统。对41例OC患者原发肿瘤手术标本的超薄切片进行电子显微镜检查。卵巢癌细胞系2008及其铂耐药变体C13用作对照。检查了七个独立的MT特征，包括MT直径、嵴结构模式、电子密度、MT分布、分布模式、卵圆形比率和MT结构。七个参数中的每一个都被赋予0至2分的评分，并汇总得出总分14分。评估了临床反应以及对铂类、紫杉烷、伊立替康和多柔比星的体外敏感性。41例中有37例可获得临床信息。24例为III期，组织学上包括16例浆液性、6例子宫内膜样和6例透明细胞癌。所有患者均接受手术，随后进行6个周期的紫杉烷和铂类化疗。15例患者有反应，22例对治疗耐药。15例有反应的病例中MT总评分为5.13±1.13（平均值±标准误），22例耐药病例中为11.41±0.43（P<0.001）。受试者工作特征（ROC）分析显示，耐药的总“临界”评分为≥10分（P<0.05；AUC=0.86），敏感性为95.5%，特异性为80.0%。MT评分系统与药物反应相关性良好，但多柔比星除外。无进展生存期（PFS）曲线显示，6个月PFS的绝对差异为10%（83%对73%），12个月PFS的绝对差异为21%（80%对59%），有利于MT评分低的患者。这种MT评分系统与临床反应以及细胞对化疗的敏感性密切相关，从而与PFS相关。
