Microsatellite analysis of the adenomatous polyposis coli (APC) gene and immunoexpression of β catenin in nephroblastoma:: a study including 83 cases treated with preoperative chemotherapy

被引:6
作者
Ramburan, A
Oladiran, F
Smith, C
Hadley, GP
Govender, D
机构
[1] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Mol Biol Res Facil, ZA-7925 Durban, South Africa
[2] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Pathol, ZA-7925 Durban, South Africa
[3] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Paediat Surg, ZA-7925 Durban, South Africa
关键词
D O I
10.1136/jcp.2004.019752
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Aims: To determine whether microsatellite mutations of the adenomatous polyposis coli (APC) gene have pathological or prognostic significance in nephroblastomas and to correlate APC alterations with beta catenin immunoexpression. Methods: One hundred nephroblastomas were analysed, 83 of which received preoperative chemotherapy. Normal and tumour DNA was isolated using standard proteinase K digestion and phenol/chloroform extraction from paraffin wax embedded tissue. Polymerase chain reaction using four APC microsatellite markers - D5S210, D5S299, D5S82, and D5S346 - was performed and the products analysed. Immunohistochemistry was performed using the LSAB kit with diaminobenzidine as chromogen. Results were correlated with clinicopathological data using the chi(2) test. Results: Allelic imbalance/loss of heterozygosity was more frequent than microsatellite instability, with 30% of cases showing allelic imbalance/loss of heterozygosity and 16% showing microsatellite instability. Although there was a significant correlation between the results for individual markers and the clinicopathological data, the overall results do not support a prognostic role for APC in nephroblastoma. Expression of beta catenin was seen in 93% of cases. Staining was predominantly membranous, with epithelium, blastema, and stroma being immunoreactive. Cytoplasmic redistribution was seen in 58% of cases, but no nuclear staining was detected. No significant associations between beta catenin expression and the clinicopathological parameters were found. Kaplan - Meier survival plots showed that patients with loss of membranous staining and pronounced cytoplasmic staining ( score, 3) had a significantly shorter survival ( p = 0.04; median survival, 5.87 months). Conclusion: Microsatellite analysis of APC and immunoexpression of beta catenin did not provide significant pathological or prognostic information in this cohort of nephroblastomas.
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页码:44 / 50
页数:7
相关论文
共 69 条
[11]   LOCALIZATION OF THE GENE FOR FAMILIAL ADENOMATOUS POLYPOSIS ON CHROMOSOME-5 [J].
BODMER, WF ;
BAILEY, CJ ;
BODMER, J ;
BUSSEY, HJR ;
ELLIS, A ;
GORMAN, P ;
LUCIBELLO, FC ;
MURDAY, VA ;
RIDER, SH ;
SCAMBLER, P ;
SHEER, D ;
SOLOMON, E ;
SPURR, NK .
NATURE, 1987, 328 (6131) :614-616
[12]   LOSS OF HETEROZYGOSITY INVOLVING THE APC AND MCC GENETIC-LOCI OCCURS IN THE MAJORITY OF HUMAN ESOPHAGEAL CANCERS [J].
BOYNTON, RF ;
BLOUNT, PL ;
YIN, J ;
BROWN, VL ;
HUANG, Y ;
TONG, Y ;
MCDANIEL, T ;
NEWKIRK, C ;
RESAU, JH ;
RASKIND, WH ;
HAGGITT, RC ;
REID, BJ ;
MELTZER, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (08) :3385-3388
[13]   WILMS-TUMOR AFTER TREATMENT [J].
BRISIGOTTI, M ;
COZZUTTO, C ;
FABBRETTI, G ;
CALIENDO, L ;
HAUPT, R ;
CORNAGLIAFERRARIS, P ;
CALLEA, F .
PEDIATRIC PATHOLOGY, 1992, 12 (03) :397-406
[14]  
Bullions Linda C., 1998, Current Opinion in Oncology, V10, P81, DOI 10.1097/00001622-199801000-00013
[15]  
Canzian F, 1996, CANCER RES, V56, P3331
[16]   MICROSATELLITE INSTABILITY IN COLORECTAL-CANCER - IMPROVED ASSESSMENT USING FLUORESCENT POLYMERASE CHAIN-REACTION [J].
CAWKWELL, L ;
DING, L ;
LEWIS, FA ;
MARTIN, I ;
DIXON, MF ;
QUIRKE, P .
GASTROENTEROLOGY, 1995, 109 (02) :465-471
[17]   Chromosome 2p, 3p, 5q and 18q status in sporadic gastric cancer [J].
Chetty, R ;
Naidoo, R ;
Tarin, M ;
Sitti, C .
PATHOLOGY, 2002, 34 (03) :275-281
[18]   POTENTIAL SOURCES OF MULTIPLE MUTATIONS IN HUMAN CANCERS [J].
CHRISTIANS, FC ;
NEWCOMB, TG ;
LOEB, LA .
PREVENTIVE MEDICINE, 1995, 24 (04) :329-332
[19]  
COPPES MJ, 1994, NEW ENGL J MED, V331, P586
[20]  
DAMICO D, 1992, CANCER RES, V52, P1996