Expression of basal cell keratin 15 and keratin 19 in oral squamous neoplasms represents diverse pathophysiologies
Expression of basal cell keratin 15 and keratin 19 in oral squamous neoplasms represents diverse pathophysiologies
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DOI：
10.14670/hh-27.949
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发表时间：
2012-07-01
影响因子：
2
通讯作者：
Yamaguchi, Akira
中科院分区：
文献类型：
--
作者：
Khanom, Rumana;Sakamoto, Kei;Yamaguchi, Akira
人上皮细胞含有角蛋白，角蛋白在分化过程中表达。根据靶细胞类型，不同类型的角蛋白表达，它们的改变似乎代表细胞特性的变化。口腔上皮的基底细胞表达角蛋白5（K5）、K14、K15和K19，但它们在肿瘤中的变化尚不清楚。为了解决这个问题，并寻求可能的诊断应用，我们研究了这些角蛋白在口腔鳞状细胞癌（OSCC）和鳞状上皮内肿瘤（SIN）的表达。43例OSCC的cDNA微阵列分析显示KRT14轻微上调，KRT15和KRT19下调，KRT5表达无变化。在每种癌症中，KRT15和KRT19的表达存在很大差异。与中分化或低分化OSCC相比，高分化OSCC倾向于表达更多的KRT15和更少的KRT19。KRT15与分化相关角蛋白KRT13呈正相关。通过免疫组织化学检查进一步研究这些观察结果。K5和K14在所有50例OSCC和50例SIN中普遍表达。K15和K19普遍下调，但在大约一半的情况下相当大的保留，并显示出不同的表达模式。K15阳性癌症倾向于显示分化良好的表型，K19阳性癌症倾向于显示更具侵袭性的肿瘤前沿。大多数K19阳性癌症似乎与SIN几乎无关。K19在SIN中持续下调，而K15主要在高级别SIN中下调。总之，K15和K19在SIN和OSCC中的表达与K5或K14不同，这反映了它们在发病机制和生物学行为上的差异，提示它们有望作为OSCC和SIN的亚分类标志物。
Human epithelium contains keratin, which is expressed during differentiation. Depending on the target cell type, different types of keratin are expressed, and their alterations seem to represent changes in cell properties. The basal cells of oral epithelium express keratin 5 (K5), K14, K15 and K19, but their alterations in tumors are unclear. To address this issue and to seek possible diagnostic application, we examined the expression of these keratins in oral squamous cell carcinoma (OSCC) and squamous intraepithelial neoplasm (SIN). cDNA microarray analysis of 43 OSCC revealed slight upregulation of KRT14, downregulation of KRT15 and KRT19, and unaltered KRT5 expression. There were great variations in KRT15 and KRT19 expression across each cancer. Well-differentiated OSCC tended to express more KRT15 and less KRT19 compared to moderately-or poorly-differentiated OSCC. KRT15 was positively correlated with differentiation-related keratin, KRT13. These observations were further investigated by immunohistochemical examination. K5 and K14 were ubiquitously expressed in all 50 OSCC and 50 SIN examined. K15 and K19 were generally downregulated, but were considerably retained in about half of the cases and showed diverse expression patterns. K15-positive cancers tended to show a well-differentiated phenotype, and K19-positive cancers tended to show more invasive tumor fronts. Most K19-positive cancers appeared to develop with little associating SIN. K19 was consistently downregulated in SIN, while K15 was downregulated mainly in high grade SIN. In summary, K15 and K19, unlike K5 or K14, are expressed variably in both SIN and OSCC, which reflects the differences in their pathogenesis and biological behaviors, suggesting their prospective applications as markers for subclassifying OSCC and SIN.