Section of Oral Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Histol Histopathol. 2012 Jul;27(7):949-59. doi: 10.14670/HH-27.949.
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.
人类上皮组织含有角蛋白，在分化过程中表达。根据靶细胞类型的不同，表达不同类型的角蛋白，其改变似乎代表了细胞特性的变化。口腔上皮的基底细胞表达角蛋白 5（K5）、K14、K15 和 K19，但它们在肿瘤中的改变尚不清楚。为了解决这个问题并寻求可能的诊断应用，我们检查了这些角蛋白在口腔鳞状细胞癌（OSCC）和鳞状上皮内瘤变（SIN）中的表达。对 43 例 OSCC 的 cDNA 微阵列分析显示，KRT14 略有上调，KRT15 和 KRT19 下调，KRT5 表达不变。每个癌症中 KRT15 和 KRT19 的表达差异很大。与中-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 与分化相关的角蛋白 KRT13 呈正相关。这些观察结果通过免疫组织化学检查进一步研究。K5 和 K14 在所有 50 例 OSCC 和 50 例 SIN 中均广泛表达。K15 和 K19 通常下调，但在大约一半的病例中保留相当多，并表现出不同的表达模式。K15 阳性的癌症往往表现出分化良好的表型，而 K19 阳性的癌症往往表现出更具侵袭性的肿瘤前缘。大多数 K19 阳性的癌症似乎在很少有相关 SIN 的情况下发展。K19 在 SIN 中持续下调，而 K15 主要在高级别 SIN 中下调。总之，与 K5 或 K14 不同，K15 和 K19 在 SIN 和 OSCC 中均呈不同程度表达，这反映了它们在发病机制和生物学行为上的差异，表明它们有望作为亚分类 OSCC 和 SIN 的标志物。
