Correlation of Allelic Loss of the P53 Gene and Tumor Grade, Stage, and Malignant Progression in Bladder Cancer

International Journal of Urology - Tập 4 Số 1 - Trang 74-78 - 1997
Masakazu Tsutsumi1, Kokichi Sugano2, Kensei Yamaguchi3, Tadao Kakizoe4, Hideyuki Akaza5
1Department of Urology, Kita-Ibaraki Municipal Hospital, Japan.
2Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan
3Department of Internal Medicine, Self Defense Force Central Hospital, Tokyo, Japan
4Department of Urology, National Cancer Center Hospital, Tokyo, Japan
5Dept. of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

Tóm tắt

Background We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. Methods LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin‐fixed, paraffin‐embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single‐strand conformation polymorphism (Non‐RI SSCP) analysis. Results Out of 40 informative samples, LOH was detected in 1 3 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 1 0 in grade 1 (0%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 1 9 (1 6%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. Conclusions The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

Từ khóa


Tài liệu tham khảo

10.1038/300143a0

10.1038/300149a0

10.1016/S0022-5347(17)35014-0

10.1002/ijc.2910570102

Fujimoto K, 1992, Frequent association of p53 gene mutation in invasive bladder cancer, Cancer Res, 52, 1393

10.1016/S0022-5347(01)67517-7

Spruck CH, 1994, Two molecular pathways to transitional cell carcinoma of the bladder, Cancer Res, 54, 784

10.1007/BF00686935

Levi S, 1991, Multiple K‐ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique, Cancer Res, 51, 3497

YamaguchiK SuganoK KyogokuA NakashimaY SaotomeK YokoyamaT YokotaT OhkuraH.PCR‐base approaches for detection of allelic loss in the p53 tumor suppresser gene in colon neoplasms.Am J Gastroenterol(in press).

10.1073/pnas.88.11.4976

10.1007/BF00210619

10.1002/(SICI)1098-2264(199603)15:3<157::AID-GCC2>3.0.CO;2-1

Sugano K, 1993, Rapid and simple detection of c‐Ki‐ras2 gene codon 12 mutations by nonradioisotopic single strand conformation polymorphism analysis, Lab Invest, 68, 361

Hosmmer DW, 1989, Applied Logistic Regression

Sossui T, 1990, Structural aspects of the p53 protein in relation to gene evolution, Oncogene, 5, 945

10.1016/S0140-6736(95)91693-8

10.1056/NEJM199411103311903

10.1016/S0090-4295(99)80216-7

10.1200/JCO.1995.13.6.1384

10.1056/NEJM199004193221607

10.1016/S0022-5347(17)35397-1

10.1093/jnci/85.1.53

10.1111/j.1464-410X.1994.tb07638.x

10.1002/ijc.2910530304

10.1056/NEJM199506013322217

10.1056/NEJM199203123261104

10.1016/0140-6736(93)92066-3

Thông tin
Thông tin xuất bản

International Journal of Urology

Tập 4 Số 1

74-78

Thông tin tác giả