Nagai M A, Pacheco M M, Brentani M M, Marques L A, Brentani R R, Ponder B A, Mulligan L M
Faculdade de Medicina, Universidade de São Paulo, Brazil.
Br J Cancer. 1994 Apr;69(4):754-8. doi: 10.1038/bjc.1994.142.
We examined loss of heterozygosity (LOH) for two loci on chromosome 17p (D17S5 and TP53), and erbB-2 gene amplification, in primary breast cancers from 67 Brazilian patients. We identified two distinct regions of LOH on chromosome 17p, one spanning TP53 and the other a more telomeric region (D17S5). Based on a short-term follow-up, Kaplan-Meier analyses of patients' disease-free survival showed that patients with LOH for D17S5, but retaining heterozygosity for TP53, were at higher risk of recurrence (P = 0.007) than those who retained heterozygosity for D17S5. Bivariate analyses indicated that patients with LOH for D17S5 alone had an increased risk of recurrence (hazard ratio = 7.2) over patients with erbB-2 amplification (hazard ratio = 3.7), when compared with patients with neither alteration (hazard ratio = 1.0). Further, lymph node-positive patients whose tumours had both LOH for D17S5 and erbB-2 gene amplification had a higher risk of recurrence than patients whose tumours had neither of these genetic alterations. Our data confirm previous reports of a putative tumour-suppressor gene, distinct from TP53, on distal chromosome 17p which is associated with breast cancer. They further suggest that LOH for loci in this region may provide an independent indicator to identify patients with poor prognosis.
我们检测了67例巴西患者原发性乳腺癌中17号染色体短臂上两个位点（D17S5和TP53）的杂合性缺失（LOH）以及erbB-2基因扩增情况。我们在17号染色体短臂上确定了两个不同的杂合性缺失区域，一个跨越TP53，另一个是更靠近端粒的区域（D17S5）。基于短期随访，对患者无病生存期的Kaplan-Meier分析显示，D17S5杂合性缺失但TP53保留杂合性的患者比D17S5保留杂合性的患者复发风险更高（P = 0.007）。双变量分析表明，与无改变的患者（风险比 = 1.0）相比，仅D17S5杂合性缺失的患者复发风险增加（风险比 = 7.2），高于erbB-2扩增的患者（风险比 = 3.7）。此外，肿瘤同时存在D17S5杂合性缺失和erbB-2基因扩增的淋巴结阳性患者比肿瘤无这些基因改变的患者复发风险更高。我们的数据证实了先前的报道，即在17号染色体远端存在一个与乳腺癌相关的假定肿瘤抑制基因，不同于TP53。这些数据还进一步表明，该区域位点的杂合性缺失可能为识别预后不良的患者提供一个独立指标。
