Yamashita H, Kobayashi S, Iwase H, Itoh Y, Kuzushima T, Iwata H, Itoh K, Naito A, Yamashita T, Masaoka A
Second Department of Surgery, Nagoya City University Medical School.
Jpn J Cancer Res. 1993 Aug;84(8):871-8. doi: 10.1111/j.1349-7006.1993.tb02060.x.
Oncogenes (c-erbB-2, c-myc, and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene (nm23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c-erbB-2, c-myc, and int-2, and expression of RB, p53(mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm23-H1 allelic loss was also studied. c-erbB-2 and c-myc amplification, loss of RB expression, p53(mutant) expression, and nm23-H1 allelic loss were also found in non-invasive carcinoma. int-2 amplification was significantly correlated with lymph node status (P = 0.02) and a significant association was found between p53(mutant) expression and tumor size (P = 0.04). c-erbB-2 amplification was strongly associated with disease-free and overall survival in multivariate analysis (P = 0.002). All of the c-erbB-2 amplified cases and all but one of the int-2 amplified cases in node-positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogen-dependent proliferation.
癌基因（c-erbB-2、c-myc以及一些与11q13病变相关的基因）、肿瘤抑制基因（视网膜母细胞瘤基因、p53）和抗转移基因（nm23/核苷二磷酸激酶）在乳腺癌进展中发挥重要作用。对77例原发性乳腺癌标本检测了c-erbB-2、c-myc和int-2的扩增情况，以及RB、p53（突变型）和NDP激酶的表达情况。还研究了nm23-H1等位基因缺失情况。在非浸润性癌中也发现了c-erbB-2和c-myc扩增、RB表达缺失、p53（突变型）表达以及nm23-H1等位基因缺失。int-2扩增与淋巴结状态显著相关（P = 0.02），并且p53（突变型）表达与肿瘤大小之间存在显著关联（P = 0.04）。在多因素分析中，c-erbB-2扩增与无病生存期和总生存期密切相关（P = 0.002）。在淋巴结阳性患者中，所有c-erbB-2扩增病例以及除1例之外的所有int-2扩增病例在切除术后2年内均复发。癌细胞可能由于多种基因改变而依次获得新的增殖途径，从而使其能够绕过雌激素依赖性增殖。
