Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Mod Pathol. 2011 Jul;24(7):963-73. doi: 10.1038/modpathol.2011.39. Epub 2011 Apr 1.
Actinic keratosis is widely believed to be a neoplastic lesion and a precursor to invasive squamous cell carcinoma. However, there has been some debate as to whether actinic keratosis is in fact actually squamous cell carcinoma and should be treated as such. As the clinical management and prognosis of patients is widely held to be different for each of these lesions, our goal was to identify unique gene signatures using DNA microarrays to discriminate among normal skin, actinic keratosis, and squamous cell carcinoma, and examine the molecular pathways of carcinogenesis involved in the progression from normal skin to squamous cell carcinoma. Formalin-fixed and paraffin-embedded blocks of skin: five normal skins (pooled), six actinic keratoses, and six squamous cell carcinomas were retrieved. The RNA was extracted and amplified. The labeled targets were hybridized to the Affymetrix human U133plus2.0 array and the acquisition and initial quantification of array images were performed using the GCOS (Affymetrix). The subsequent data analyses were performed using DNA-Chip Analyzer and Partek Genomic Suite 6.4. Significant differential gene expression (>2 fold change, P<0.05) was seen with 382 differentially expressed genes between squamous cell carcinoma and normal skin, 423 differentially expressed genes between actinic keratosis and normal skin, and 9 differentially expressed genes between actinic keratosis and squamous cell carcinoma. The differentially expressed genes offer the possibility of using DNA microarrays as a molecular diagnostic tool to distinguish between normal skin, actinic keratosis, and squamous cell carcinoma. In addition, the differentially expressed genes and their molecular pathways could be potentially used as prognostic markers or targets for future therapeutic innovations.
光化性角化病被广泛认为是一种肿瘤性病变，是侵袭性鳞状细胞癌的前身。然而，关于光化性角化病实际上是否是鳞状细胞癌，是否应如此对待，一直存在一些争议。由于这些病变的临床管理和预后被广泛认为是不同的，我们的目标是使用 DNA 微阵列识别独特的基因特征，以区分正常皮肤、光化性角化病和鳞状细胞癌，并研究从正常皮肤到鳞状细胞癌癌变过程中涉及的分子途径。我们从福尔马林固定和石蜡包埋的皮肤块中获取了 5 份正常皮肤（合并）、6 份光化性角化病和 6 份鳞状细胞癌。提取并扩增了 RNA。将标记的靶标与 Affymetrix 人类 U133plus2.0 阵列杂交，并使用 GCOS（Affymetrix）进行阵列图像的获取和初步定量。随后使用 DNA-Chip Analyzer 和 Partek Genomic Suite 6.4 进行数据分析。在鳞状细胞癌与正常皮肤之间，有 382 个差异表达基因，在光化性角化病与正常皮肤之间，有 423 个差异表达基因，在光化性角化病与鳞状细胞癌之间，有 9 个差异表达基因。差异表达基因提供了使用 DNA 微阵列作为分子诊断工具来区分正常皮肤、光化性角化病和鳞状细胞癌的可能性。此外，差异表达基因及其分子途径可以作为潜在的预后标志物或未来治疗创新的靶点。
