St John's Institute of Dermatology, King's College London, Guy's Campus, London, UK.
Histopathology. 2010 Jan;56(1):91-9. doi: 10.1111/j.1365-2559.2009.03442.x.
Although dermatopathology and molecular biology are often considered to be separate laboratory disciplines, the respective approaches are far from mutually exclusive. This is certainly the case for understanding the pathology of blistering skin diseases, both acquired and inherited. For example, in toxic epidermal necrolysis, dermatopathology in isolation may provide few clues to disease pathogenesis. There is widespread keratinocyte apoptosis and a variable infiltrate of cytotoxic T cells, but morphology alone offers little insight into what causes the epidermal destruction. In contrast, molecular biology studies have revealed several key processes that help explain the keratinocyte death, including increased expression of death receptors and their ligands on keratinocyte cell membranes as well as the presence of local or systemic immunocyte-derived cytolytic granules. For some inherited blistering diseases, however, such as epidermolysis bullosa, the molecular pathology is complex and difficult to unravel in isolation, yet the addition of dermatopathology is helpful in focusing molecular investigations. Notably, immunolabelling of cell adhesion proteins using specific antibody probes can identify reduced or absent immunoreactivity for candidate genes/proteins. Bridging dermatopathology and molecular biology investigations facilitates a greater understanding of disease processes, improves diagnostic accuracy, and provides a basis for the development and appraisal of new treatments.
尽管皮肤病理学和分子生物学通常被认为是两个独立的实验室学科，但它们的方法远非相互排斥。对于理解获得性和遗传性水疱性皮肤病的病理学来说，情况就是如此。例如，在中毒性表皮坏死松解症中，单独的皮肤病理学可能对疾病发病机制提供很少的线索。存在广泛的角质形成细胞凋亡和可变的细胞毒性 T 细胞浸润，但仅形态学并不能深入了解是什么导致了表皮破坏。相比之下，分子生物学研究揭示了几个有助于解释角质形成细胞死亡的关键过程，包括角质形成细胞膜上死亡受体及其配体的表达增加，以及局部或全身免疫细胞衍生的细胞溶解颗粒的存在。然而，对于一些遗传性水疱性疾病，如大疱性表皮松解症，分子病理学非常复杂，难以单独阐明，但添加皮肤病理学有助于集中进行分子研究。值得注意的是，使用特定抗体探针对细胞黏附蛋白进行免疫标记，可以识别候选基因/蛋白的减少或缺失免疫反应性。将皮肤病理学和分子生物学研究联系起来，可以更好地了解疾病过程，提高诊断准确性，并为新治疗方法的开发和评估提供基础。
