Borg A, Sigurdsson H, Clark G M, Fernö M, Fuqua S A, Olsson H, Killander D, McGurie W L
Department of Oncology, University Hospital, Lund, Sweden.
Br J Cancer. 1991 Jan;63(1):136-42. doi: 10.1038/bjc.1991.28.
The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome 11q13 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0.001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HST1 amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0.015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 11q13 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at 11q13 is due to the activity of INT2, HST1 or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.
人类原癌基因INT2（与小鼠INT2基因同源，与病毒诱导的乳腺癌有关）已被定位到11号染色体q13区，并且发现它与HST1原癌基因等基因共享带定位。这两个基因都是成纤维细胞生长因子家族的成员。在本研究中，使用狭缝印迹和Southern印迹分析发现，在311例浸润性人类乳腺癌中有27例（9%）存在INT2/HST1基因的共扩增（2 - 15个拷贝）。扩增与肿瘤大小、腋窝淋巴结状态或疾病分期均无关，与患者年龄或绝经状态也无关。然而，与65%的未扩增病例相比，27例扩增肿瘤中有26例（96%）通常为强雌激素受体阳性（P = 0.001）。这些发现与之前在同一组肿瘤中观察到的HER - 2/neu原癌基因扩增与晚期和类固醇受体阴性的强相关性形成鲜明对比。与基因未扩增的患者相比，INT2/HST1基因扩增的乳腺癌患者无病生存期明显更短（P = 0.015，中位随访45个月）。这种相关性仅限于淋巴结阴性的患者，并且在多变量分析中仍然存在。未发现与乳腺癌生存率有显著相关性。结论是，乳腺癌中11q13区域的扩增发生在侵袭性肿瘤的一个特定亚组中，与HER - 2/neu扩增所确定的亚组有很大不同。11q13处扩增基因的选择是由于INT2、HST1或另一个尚未确定的邻近基因的活性，这一点仍有待证明。然而，这些结果在区分一组淋巴结阴性乳腺癌患者以进行更强化治疗方面可能具有临床价值。
