C-MYC AMPLIFICATION IS AN INDEPENDENT PROGNOSTIC FACTOR IN POSTMENOPAUSAL BREAST-CANCER
C-MYC AMPLIFICATION IS AN INDEPENDENT PROGNOSTIC FACTOR IN POSTMENOPAUSAL BREAST-CANCER
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DOI：
10.1002/ijc.2910510504
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发表时间：
1992-07-09
影响因子：
6.4
通讯作者：
SIGURDSSON, H
中科院分区：
文献类型：
--
作者：
BORG, A;BALDETORP, B;SIGURDSSON, H
分析了311例原发性乳腺癌的c-myc原癌基因，发现其中8%的c-myc原癌基因扩增，通常在适度增加的拷贝数（2-5个拷贝）。在所有分析的肿瘤中，邻近的pvt基因与c-myc共扩增。C-myc扩增与高S期分数和c-erbB-2原癌基因扩增显著相关。c-myc扩增与淋巴结转移、晚期、DNA非二倍体和绝经前状态之间存在弱相关性，但与肿瘤大小、雌激素受体或孕激素受体状态或int-2扩增无关。 C-myc扩增，尤其是高拷贝数（>5拷贝），与乳腺癌早期复发和死亡显著相关， 淋巴结阴性和淋巴结阳性两个亚类在绝经后患者中观察到与不良临床结局的特别强的相关性（p > 0.0005），这种相关性在多变量生存分析中持续存在。我们的结论是，c-myc的激活确实与乳腺癌的快速增长和进展。另一方面，基因扩增是相对罕见的，主要发生在低拷贝数，这意味着肿瘤是异质性的细胞克隆窝藏c-myc扩增。免疫组化评估将更准确地说明c-myc激活在人类乳腺癌中的重要性。然而，c-myc转录和翻译的明显不稳定性表明，c-myc不是用于常规目的的合适的预后标志物。
The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-nod metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (>5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p > 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.