Bevilacqua G, Sobel M E, Liotta L A, Steeg P S
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Res. 1989 Sep 15;49(18):5185-90.
Expression of a recently identified murine gene, nm23, has been previously proposed to be inversely correlated to tumor metastatic potential in rodent model systems. The present study was designed to investigate whether nm23 RNA was detectable in human tumor tissue, and if it was differentially expressed. nm23 RNA levels in 27 human primary infiltrating ductal breast carcinomas were determined by using Northern blots or in situ hybridization. These data were compared to traditional histopathological indicators of metastatic potential, including the number of involved (tumor bearing) lymph nodes, grade of differentiation, and hormone receptor status. A striking consistency was observed in all tumors from patients with involved lymph nodes. Using Northern blot or in situ hybridizations, all of these tumors expressed low levels of nm23 RNA. Quantitative in situ hybridization on tumors from patients with 0 involved lymph nodes identified two groups: (a) approximately 75% contained high nm23 RNA levels, and (b) 25% contained significantly (alpha = 0.05) lower nm23 RNA levels. Low nm23 RNA levels in the 0 involved lymph node tumors were accompanied by two additional histopathological indicators of high metastatic potential, low nuclear and cytoplasmic estrogen receptor content, and poorly differentiated histological grade. In contrast, none of the high nm23 RNA level tumors were both receptor negative and poorly differentiated. We conclude that nm23 RNA levels are differentially expressed in human breast tumors, and that low nm23 RNA levels are associated with histopathological indication of high metastatic potential. Short term (median follow-up of 16 months) clinical course data were consistent with nm23 RNA levels, in that 2 of 11 low nm23 RNA content patients (including one from the 0 involved lymph node group) developed metastases, while none of the high nm23 RNA patients have experienced recurrent disease.
最近发现的一种小鼠基因nm23的表达，先前已有人提出在啮齿动物模型系统中它与肿瘤转移潜能呈负相关。本研究旨在调查nm23 RNA在人类肿瘤组织中是否可检测到，以及它是否存在差异表达。通过Northern印迹法或原位杂交法测定了27例人类原发性浸润性导管乳腺癌中的nm23 RNA水平。将这些数据与转移潜能的传统组织病理学指标进行比较，这些指标包括受累（有肿瘤）淋巴结的数量、分化程度以及激素受体状态。在所有有受累淋巴结患者的肿瘤中观察到了显著的一致性。使用Northern印迹法或原位杂交法，所有这些肿瘤均表达低水平的nm23 RNA。对无受累淋巴结患者的肿瘤进行定量原位杂交，确定了两组：（a）约75%含有高水平的nm23 RNA，（b）25%含有显著（α = 0.05）较低水平的nm23 RNA。无受累淋巴结肿瘤中nm23 RNA水平较低伴随着另外两个高转移潜能的组织病理学指标，即细胞核和细胞质雌激素受体含量低以及组织学分级差。相比之下，高水平nm23 RNA的肿瘤均无受体阴性且分化差的情况。我们得出结论，nm23 RNA水平在人类乳腺肿瘤中存在差异表达，且低水平的nm23 RNA与高转移潜能的组织病理学指标相关。短期（中位随访16个月）临床病程数据与nm23 RNA水平一致，11例nm23 RNA含量低的患者中有2例（包括1例来自无受累淋巴结组的患者）发生了转移，而高水平nm23 RNA的患者均未出现复发病例。
