Section of Oral Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Histopathology. 2011 Mar;58(4):531-42. doi: 10.1111/j.1365-2559.2011.03759.x. Epub 2011 Mar 3.
This study aimed to identify relevant keratin subtypes that may associate with the pathogenesis of oral epithelial neoplasms.
Expression of all the keratin subtypes was examined by cDNA microarray analysis of 43 oral squamous cell carcinoma (OSCC) cases. Immunohistochemical expression of the major keratins was examined in 100 OSCC and oral epithelial dysplasia (OED) cases. Many changes in keratin expression were observed and, significantly, consistent down-regulation of keratin 4 (K4) and K13 expression was observed. Aberrant expression of K4 and K13 was associated with morphological changes in the affected oral epithelium. Experiments with cell cultures transfected with various keratin subtypes suggested that alterations in keratin subtype expression can cause changes in cell shape and movement.
Aberrant expression of K4 and K13, which are the dominant pair of differentiation-related keratins in oral keratinocytes, indicates dysregulation of epithelial differentiation in OSCC and OED. These keratins, especially K4, may be useful for pathological diagnosis. We propose that the aberrant expression of K4 and K13 and concomitant up-regulation of the other keratins may be one of the causative factors for morphological alterations in the affected epithelium.
本研究旨在鉴定可能与口腔上皮肿瘤发病机制相关的角质蛋白亚型。
通过对 43 例口腔鳞状细胞癌（OSCC）病例的 cDNA 微阵列分析，检测了所有角质蛋白亚型的表达情况。在 100 例口腔上皮异型增生（OED）和口腔鳞状细胞癌（OSCC）病例中，检测了主要角蛋白的免疫组织化学表达。观察到许多角质蛋白表达的变化，并且明显观察到角蛋白 4（K4）和 K13 的表达持续下调。K4 和 K13 的异常表达与受影响的口腔上皮形态变化有关。用转染不同角质蛋白亚型的细胞培养实验表明，角质蛋白亚型表达的改变可导致细胞形状和运动的改变。
在口腔角质形成细胞中占主导地位的分化相关角蛋白 K4 和 K13 的异常表达表明，在 OSCC 和 OED 中上皮分化失调。这些角蛋白，尤其是 K4，可能对病理诊断有用。我们提出，K4 和 K13 的异常表达以及其他角蛋白的伴随上调可能是受影响上皮形态改变的一个原因。
