Redline R W, Hudock P, MacFee M, Patterson P
Department of Pathology, Case Western Reserve University, Cleveland, Ohio.
Lab Invest. 1994 Nov;71(5):663-70.
Homeobox (HOX) genes of the ANT-C/BX-C type control rostral-caudal patterning during embryogenesis. Previous work has shown that tissues express unique HOX gene expression profiles that persist upon transplantation to distant sites. These properties suggest that analysis of HOX genes may be useful for the diagnosis and evaluation of primary and metastatic tumors.
We analyzed normal and neoplastic tissues for the expression of three AbdB-type HOX genes; HOXD10, HOXA9, and HOXC9 to evaluate three hypotheses: (a) that tumors express HOX genes found in their tissue of origin, (b) that metastatic tumors continue to express HOX genes found in the primary tumor, and (c) that the level of HOX expression is related to tumor grade.
Malignant tumors gave consistent patterns of HOX gene expression that paralleled their tissues of origin. Normal kidney and Wilm's tumors expressed all three genes. Other renal tumors expressed distinct permutations of the three genes. One epithelial Wilm's tumor expressed only an aberrant 0.3 kb HOXD10 transcript. Outside of the kidney, HOXD10 was most characteristic of uterine tumors, HOXA9 of colonic adenocarcinomas, and HOXC9 of two groups of tumors: neoplasms derived from neural crest and mesenchymal tumors derived from intermediate mesoderm. Metastatic tumors retained their HOX gene expression profiles and did not express HOX genes transcribed at the site of metastasis. While modulation of HOX gene expression was observed in some poorly differentiated tumors this was not a consistent measure of tumor grade.
HOX gene profile was a reliable indicator of histologic subtype in a variety of tumors and in selected cases provided useful diagnostic information. Persistent expression in metastatic tumors confirmed that HOX expression profiles are potentially useful for diagnosing tumors of unknown origin. Continued analysis of the relationship between level of expression and tumor grade/behavior is indicated.
ANT-C/BX-C 型同源框（HOX）基因在胚胎发生过程中控制头尾模式形成。先前的研究表明，组织表达独特的 HOX 基因表达谱，且在移植到远处部位后仍持续存在。这些特性表明，分析 HOX 基因可能有助于原发性和转移性肿瘤的诊断和评估。
我们分析了正常组织和肿瘤组织中三种 AbdB 型 HOX 基因（HOXD10、HOXA9 和 HOXC9）的表达，以评估三个假设：（a）肿瘤表达其起源组织中发现的 HOX 基因；（b）转移性肿瘤继续表达原发性肿瘤中发现的 HOX 基因；（c）HOX 表达水平与肿瘤分级相关。
恶性肿瘤呈现出与其起源组织平行的一致 HOX 基因表达模式。正常肾脏和肾母细胞瘤表达所有三种基因。其他肾脏肿瘤表达这三种基因的不同组合。一个上皮性肾母细胞瘤仅表达异常的 0.3 kb HOXD10 转录本。在肾脏之外，HOXD10 最具子宫肿瘤特征，HOXA9 是结肠腺癌的特征，HOXC9 是两组肿瘤的特征：源自神经嵴的肿瘤和源自中间中胚层的间充质肿瘤。转移性肿瘤保留其 HOX 基因表达谱，且不表达在转移部位转录的 HOX 基因。虽然在一些低分化肿瘤中观察到 HOX 基因表达的调节，但这并不是肿瘤分级的一致指标。
HOX 基因谱是多种肿瘤组织学亚型的可靠指标，在某些情况下提供了有用的诊断信息。转移性肿瘤中的持续表达证实，HOX 表达谱可能有助于诊断来源不明的肿瘤。表明需要继续分析表达水平与肿瘤分级/行为之间的关系。
