Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Iwate, Japan.
J Oral Pathol Med. 2013 Feb;42(2):133-9. doi: 10.1111/j.1600-0714.2012.01182.x. Epub 2012 Jun 5.
The product of the Wilms' tumor gene, WT1 protein, is a tumor antigen for various kinds of cancer, and WT1 peptide-based cancer immunotherapy is widely anticipated as a new possibility for cancer treatment. The aim of this study was to investigate the expression of WT1 from quantitative and morphological perspectives in oral squamous cell carcinoma (OSCC), the most widespread malignant neoplasm of the oral cavity.
Six OSCC cell lines and tissue sections from 29 OSCC patients were analyzed. To detect WT1 expression, reverse transcription-polymerase chain reaction analysis (RT-PCR), real-time PCR, Western blots, and immunofluorescence flow cytometry for WT1 were performed on the cell lines, and immunohistochemistry and fluorescence in situ hybridization (FISH) were performed on the tissue sections.
WT1 mRNA was found overexpressed in one of the six OSCC cell lines, with expression levels higher than that seen in human leukemia cell line (K562). Immunohistochemical analysis of tissue sections showed overexpression of WT1 protein in two patients, concentrated mainly in the cytoplasm of the outer one to three cell layers of the cancer nests. This was consistent with the expression of WT1 mRNA observed by FISH. Meanwhile, WT1 was not detected on normal oral epithelium. WT1 protein was detected on actively proliferating cancer nests and even on elongated epithelial ridge where new droplet-cancer-nests were being formed and starting infiltration toward subepithelial layer.
The results suggest that WT1 plays an important role in the pathogenesis of some types of OSCC, particularly in proliferation of the cancer cells.
Wilms 瘤基因的产物 WT1 蛋白是多种癌症的肿瘤抗原,基于 WT1 肽的癌症免疫疗法被广泛认为是癌症治疗的新可能性。本研究旨在从定量和形态学角度研究 WT1 在口腔鳞状细胞癌(OSCC)中的表达,OSCC 是口腔最常见的恶性肿瘤。
分析了 6 种 OSCC 细胞系和 29 例 OSCC 患者的组织切片。为了检测 WT1 的表达,对细胞系进行了逆转录聚合酶链反应分析(RT-PCR)、实时 PCR、Western blot 和 WT1 免疫荧光流式细胞术,对组织切片进行了免疫组织化学和荧光原位杂交(FISH)。
在 6 种 OSCC 细胞系中的一种中发现 WT1 mRNA 过表达,其表达水平高于人白血病细胞系(K562)。组织切片的免疫组织化学分析显示,2 例患者 WT1 蛋白过表达,主要集中在癌巢外一至三层细胞的细胞质中。这与 FISH 观察到的 WT1 mRNA 表达一致。同时,WT1 在正常口腔上皮中未检测到。WT1 蛋白在活跃增殖的癌巢中检测到,甚至在形成新的滴状癌巢并开始向黏膜下层浸润的伸长上皮嵴上也检测到。
这些结果表明,WT1 在某些类型的 OSCC 的发病机制中发挥重要作用,特别是在癌细胞的增殖中。