Expression of Wilms' tumor 1 (WT1) in oral squamous cell carcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The results suggest that WT1 plays an important role in the pathogenesis of some types of OSCC, particularly in proliferation of the cancer cells.
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Iwate, Japan. toshi_m@sea.plala.or.jp
Toshinari
T
Mikami
Tomohiro
T
Hada
Naoyuki
N
Chosa
Akira
A
Ishisaki
Harumi
H
Mizuki
Yasunori
Y
Takeda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D003593:Cytoplasm / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000032:analysis*
D025721:WT1 Proteins