Department of Laboratory Medicine, Center for Molecular Pathology, Skåne University Hospital Malmö, Malmö, Sweden.
Ups J Med Sci. 2012 May;117(2):217-24. doi: 10.3109/03009734.2012.659294. Epub 2012 Feb 29.
The differentiation stage of tumors is a central aspect in the histopathological classification of solid malignancies. The differentiation stage is strongly associated with tumor behavior, and generally an immature tumor is more aggressive than the more differentiated counterpart. While this is common knowledge in surgical pathology, the contribution of differentiation-related gene expression and functions to tumor behavior is often overlooked in the experimental, tumor biological setting. The mechanisms by which tumor cell differentiation stages are perturbed or affected are poorly explored but have recently come into focus with the introduction.of the tumor stem cell concept. While developmental biologists view the differentiation as a unidirectional event, pathologists and tumor biologists have introduced the concept of dedifferentiation to explain phenotypic changes occurring in solid tumors. In this review we discuss the impact of the tumor cell differentiation stage as used in surgical pathology. We further discuss knowledge gained from exploring the molecular basis of the differentiation and dedifferentiation processes in neuroblastoma and breast cancer, two tumor forms where the tumor cell differentiation concept is used in the clinical diagnostic work and where the tumor stem cell theory has been applied.
肿瘤的分化阶段是实体恶性肿瘤组织病理学分类的一个核心方面。分化阶段与肿瘤行为密切相关，一般来说，不成熟的肿瘤比分化程度更高的肿瘤更具侵袭性。虽然这在外科病理学中是常识，但在实验性、肿瘤生物学环境中，分化相关基因表达和功能对肿瘤行为的贡献往往被忽视。肿瘤细胞分化阶段受到干扰或影响的机制尚未得到充分探索，但随着肿瘤干细胞概念的引入，这一问题最近引起了关注。虽然发育生物学家将分化视为一个单向事件，但病理学家和肿瘤生物学家引入了去分化的概念，以解释实体肿瘤中发生的表型变化。在这篇综述中，我们讨论了外科病理学中使用的肿瘤细胞分化阶段的影响。我们进一步讨论了从探索神经母细胞瘤和乳腺癌中分化和去分化过程的分子基础中获得的知识，这两种肿瘤形式在临床诊断工作中使用肿瘤细胞分化概念，并且已经应用了肿瘤干细胞理论。
