Ra Seong H, Su Albert, Li Xinmin, Zhou Jaime, Cochran Alistair J, Kulkarni Rajan P, Binder Scott W
1] San Diego Pathology Medical Group, San Diego, CA, USA [2] Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Mod Pathol. 2015 Jun;28(6):799-806. doi: 10.1038/modpathol.2015.5. Epub 2015 Feb 13.
Keratoacanthoma is a controversial entity. Some consider keratoacanthoma as a variant of squamous cell carcinoma, whereas others see it as a distinct self-resolving squamoproliferative lesion. Our objective is to examine the relationship of keratoacanthoma with squamous cell carcinoma and normal skin by using DNA microarrays. DNA microarray studies were performed on formalin-fixed and paraffin-embedded blocks from ten cases of actinic keratoacanthoma utilizing the U133plus2.0 array. These results were compared with our previously developed microarray database of ten squamous cell carcinoma and ten normal skin samples. Keratoacanthoma demonstrated 1449 differentially expressed genes in comparison with squamous cell carcinoma (>5-fold change: P<0.01) with 908 genes upregulated and 541 genes downregulated. Keratoacanthoma showed 2435 differentially expressed genes in comparison with normal skin (>5-fold change: P<0.01) with 1085 genes upregulated and 1350 genes downregulated. The most upregulated genes, comparing keratoacanthoma with normal skin included MALAT1, S100A8, CDR1, TPM4, and CALM1. The most downregulated genes included SCGB2A2, DCD, THRSP, ADIPOQ, adiponectin, and ADH1B. The molecular biological pathway analysis comparing keratoacanthoma with normal skin showed that cellular development, cellular growth and proliferation, cell death/apoptosis, and cell cycle pathways are prominently involved in the pathogenesis of keratoacanthoma. The most enriched canonical pathways were clathrin-mediated endocytosis signaling, molecular mechanisms of cancer and integrin signaling. The distinctive gene expression profile of keratoacanthoma reveals that it is molecularly distinct from squamous cell carcinoma. The molecular pathways and genes differentially expressed in comparing keratoacanthoma with normal skin suggest that keratoacanthoma is a neoplasm that can regress due to upregulation of the cell death/apoptosis pathway.
角化棘皮瘤是一个存在争议的实体。一些人认为角化棘皮瘤是鳞状细胞癌的一种变体,而另一些人则将其视为一种独特的可自行消退的鳞状上皮增生性病变。我们的目的是通过使用DNA微阵列来研究角化棘皮瘤与鳞状细胞癌以及正常皮肤之间的关系。利用U133plus2.0阵列对10例光化性角化棘皮瘤的福尔马林固定石蜡包埋组织块进行了DNA微阵列研究。将这些结果与我们之前建立的包含10例鳞状细胞癌和10例正常皮肤样本的微阵列数据库进行比较。与鳞状细胞癌相比,角化棘皮瘤显示出1449个差异表达基因(变化>5倍:P<0.01),其中908个基因上调,541个基因下调。与正常皮肤相比,角化棘皮瘤显示出2435个差异表达基因(变化>5倍:P<0.01),其中1085个基因上调,1350个基因下调。将角化棘皮瘤与正常皮肤相比,上调最明显的基因包括MALAT1、S100A8、CDR1、TPM4和CALM1。下调最明显的基因包括SCGB2A2、DCD、THRSP、ADIPOQ、脂联素和ADH1B。将角化棘皮瘤与正常皮肤进行比较的分子生物学通路分析表明,细胞发育、细胞生长和增殖、细胞死亡/凋亡以及细胞周期通路在角化棘皮瘤的发病机制中显著相关。最富集的经典通路是网格蛋白介导的内吞信号通路、癌症分子机制和整合素信号通路。角化棘皮瘤独特的基因表达谱表明它在分子水平上与鳞状细胞癌不同。在将角化棘皮瘤与正常皮肤进行比较时差异表达的分子通路和基因表明,角化棘皮瘤是一种由于细胞死亡/凋亡通路上调而可消退的肿瘤。