bcl-2 Overexpression combined with p53 protein accumulation correlates with hormone-refractory prostate cancer

被引:110
作者
Apakama, I
Robinson, MC
Walter, NM
Charlton, RG
Royds, JA
Fuller, CE
Neal, DE
Hamdy, FC
机构
[1] UNIV NEWCASTLE UPON TYNE,UROL UNIT,NEWCASTLE TYNE NE7 7DN,TYNE & WEAR,ENGLAND
[2] FREEMAN RD HOSP,DEPT PATHOL,NEWCASTLE TYNE NE7 7DN,TYNE & WEAR,ENGLAND
[3] UNIV SHEFFIELD,DEPT PATHOL,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND
关键词
prostate cancer; apoptosis; p53; bcl-2; tumour-suppressor gene; oncogene;
D O I
10.1038/bjc.1996.526
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Seventy-seven men with histologically proven and newly diagnosed prostate cancer were investigated for the presence of bcl-2 protein overexpression and p53 protein accumulation by immunohistochemistry. Forty-five men had evidence of locally advanced and metastatic disease and were treated by means of hormone manipulation. Twenty-eight patients either failed to respond to initial hormone manipulation or relapsed within 37 months from diagnosis (median 20 months). Of the 77 cancers, 37 (48%) showed bcl-2 overexpression at diagnosis. Twenty-seven of those were treated with androgen ablation and 20 (74%) had hormone-refractory disease (P = 0.0128). Twenty-three of 77 men (29.8%) had nuclear staining for p53 protein. Twenty-one of those were treated with hormone manipulation and 14 (66.6%) showed hormone resistance (P = 0.0012). Seventeen patients had both bcl-2 overexpression and p53 protein accumulation, 16 of whom were hormonally treated. with 13 (81.2%) having hormone-refractory disease (P < 0.0001). These findings suggest that the combined detection of p53 protein accumulation and bcl-2 overexpression may be useful in predicting hormone resistance in prostate cancer. By deregulating programmed cell death. alterations in these genes may prevent patients from responding to androgen ablation. or allow them to escape hormonal control of the disease.
引用
收藏
页码:1258 / 1262
页数:5
相关论文
共 36 条
[1]
FREQUENCY OF APOPTOTIC BODIES POSITIVELY CORRELATES WITH GLEASON GRADE IN PROSTATE-CANCER [J].
AIHARA, M ;
TRUONG, LD ;
DUNN, JK ;
WHEELER, TM ;
SCARDINO, PT ;
THOMPSON, TC .
HUMAN PATHOLOGY, 1994, 25 (08) :797-801
[2]
IMMUNOHISTOCHEMICAL DETERMINATION OF P53 PROTEIN NUCLEAR ACCUMULATION IN PROSTATIC ADENOCARCINOMA [J].
APRIKIAN, AG ;
SARKIS, AS ;
FAIR, WR ;
ZHANG, ZF ;
FUKS, Z ;
CORDONCARDO, C .
JOURNAL OF UROLOGY, 1994, 151 (05) :1276-1280
[3]
EVALUATION OF 6 ANTIBODIES FOR IMMUNOHISTOCHEMISTRY OF MUTANT P53 GENE-PRODUCT IN ARCHIVAL COLORECTAL NEOPLASMS [J].
BAAS, IO ;
MULDER, JWR ;
OFFERHAUS, GJA ;
VOGELSTEIN, B ;
HAMILTON, SR .
JOURNAL OF PATHOLOGY, 1994, 172 (01) :5-12
[4]
CELL-PROLIFERATION, DNA-REPAIR, AND P53 FUNCTION ARE NOT REQUIRED FOR PROGRAMMED DEATH OF PROSTATIC GLANDULAR CELLS INDUCED BY ANDROGEN ABLATION [J].
BERGES, RR ;
FURUYA, Y ;
REMINGTON, L ;
ENGLISH, HF ;
JACKS, T ;
ISAACS, JT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (19) :8910-8914
[5]
MOLECULAR THEMES IN ONCOGENESIS [J].
BISHOP, JM .
CELL, 1991, 64 (02) :235-248
[6]
APOPTOTIC CELL-DEATH INDUCED BY C-MYC IS INHIBITED BY BCL-2 [J].
BISSONNETTE, RP ;
ECHEVERRI, F ;
MAHBOUBI, A ;
GREEN, DR .
NATURE, 1992, 359 (6395) :552-554
[7]
BRANDSTROM A, 1994, CANCER RES, V54, P3594
[8]
COLOMBEL M, 1992, CANCER RES, V52, P4313
[9]
COLOMBEL M, 1993, AM J PATHOL, V143, P390
[10]
FISHER CJ, 1994, BRIT J CANCER, V69, P20