Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer

被引:78
作者
Mano, Y [1 ]
Kikuchi, Y [1 ]
Yamamoto, K [1 ]
Kita, T [1 ]
Hirata, J [1 ]
Tode, T [1 ]
Ishii, K [1 ]
Nagata, I [1 ]
机构
[1] Natl Def Med Coll, Dept Obstet & Gynecol, Tokorozawa, Saitama 3598513, Japan
关键词
bcl-2; cisplatin; ovarian cancer; p53; MDM-2; cisplatin resistance; apoptosis;
D O I
10.1016/S0959-8049(99)00124-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2, was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P= 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1214 / 1219
页数:6
相关论文
共 25 条
[1]   Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer [J].
Bauer, JJ ;
Sesterhenn, IA ;
Mostofi, FK ;
McLeod, DG ;
Srivastava, S ;
Moul, JW .
JOURNAL OF UROLOGY, 1996, 156 (04) :1511-1516
[2]   APOPTOSIS AND DISEASE [J].
CARSON, DA ;
RIBEIRO, JM .
LANCET, 1993, 341 (8855) :1251-1254
[3]   INTERACTIONS BETWEEN P53 AND MDM2 IN A MAMMALIAN-CELL CYCLE CHECKPOINT PATHWAY [J].
CHEN, CY ;
OLINER, JD ;
ZHAN, QM ;
FORNACE, AJ ;
VOGELSTEIN, B ;
KASTAN, MB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (07) :2684-2688
[4]  
Diebold J, 1996, AM J CLIN PATHOL, V105, P341
[5]   DRUG-TARGET INTERACTIONS - ONLY THE 1ST STEP IN THE COMMITMENT TO A PROGRAMMED CELL-DEATH [J].
DIVE, C ;
HICKMAN, JA .
BRITISH JOURNAL OF CANCER, 1991, 64 (01) :192-196
[6]   PURIFICATION AND CHARACTERIZATION OF THE BCL-2 PROTEIN [J].
HALDAR, S ;
JENA, N ;
DUBOIS, GC ;
TAKAYAMA, S ;
REED, JC ;
FU, SS ;
CROCE, CM .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1994, 315 (02) :483-488
[7]   EXPRESSION AND PROGNOSTIC-SIGNIFICANCE OF BCL-2 IN OVARIAN-TUMORS [J].
HENRIKSEN, R ;
WILANDER, E ;
OBERG, K .
BRITISH JOURNAL OF CANCER, 1995, 72 (05) :1324-1329
[8]  
Herod JJO, 1996, CANCER RES, V56, P2178
[9]  
KONDO S, 1995, ONCOGENE, V10, P2001
[10]  
LU QL, 1994, J CELL SCI, V107, P363