Configuring the Expression of Wilms Tumor 1 in Oral Squamous Cell Carcinoma and Its Relationship with Clinicopathologic Features

    

    

    Figure 2:  Immunohistochemical analysis of WT1 expression at
400×magnification.
This sample was positive for WT1 expression.
    
    

This study aimed to investigate the expression of WT1 in OSCC and its relationship with histopathologic grade. The three cases with WT1 expression were all well-differentiated. According to a regionalgrade chart, eight cases were in the buccal area with a histopathologic grade of well-differentiated. Of 20 cases in the tongue, 15 were welldifferentiated, and 5 had a moderate grade. Thirteen cases were from the gingival area, of which, 10 had a well-differentiated grade, 1 had a reported moderate grade, and 2 were poorly-differentiated. There was no statistically significant difference between the location and grade of the tumors (P = 0.26).

In evaluating the relationship between WT1 expression and involved area, the cases with WT1 expression were in the tongue, buccal area, and conflict zone of the oral floor (one each). No WT1 positive samples came from the gingiva.

We found no significant relationship between WT1 expression and conflict region (P = 0.927).

One WT1 positive sample was from a woman, and the remaining two came from men. There was no significant correlation between gender and WT1 expression (P = 0.715).

Of the 16 samples from women, 12 were well-differentiated and 4 had a moderate histopathology grade. Of the 29 samples from men, 24 were well-differentiated, 3 had a moderately-differentiated grade, and 2 had a histopathologic grade of poor. There was no significant relationship between gender and histopathologic grade (P = 0.958). There was also no significant relation between histopathologic grade and WT1 expression (P = 0.044).

Discussion

Squamous cell carcinoma is the most common tumor in head and neck malignancies. The latest advances in the treatment of oral cancer have not significantly enhanced survival, and only about half of all individuals diagnosed with head and neck cancer will survive five years [15].

Recently, WT1 peptide-based cancer immunotherapy has emerged as a possible new cancer treatment, and over the last eight years, clinical trials of WT1 peptide-based cancer immunotherapies have shown effective clinical responses for specific types of cancers. Oka et al. performed a phase I clinical trial for a WT1-based vaccine in patients with different types of cancer and confirmed that, except for a local inflammatory response with erythema at the injection site, there were no observable damages to healthy tissues. Morita et al. evaluated the toxicity of a weekly treatment of WT1 injection in patients with solid malignancies and concluded that WT1 peptide-based immunotherapy is acceptable for patients. Further understanding of the role of WT1 in OSCC, however, will facilitate the development of new treatment strategies [13,15,16].

In another study, Oji et al. examined the expression levels of WT1 mRNA in tissue samples obtained from patients diagnosed with head and neck SCCs using real-time PCR and found that all 4 cases in the mouth floor, 5 of 9 cases in the gingiva, and 17 of 25 cases in the tongue displayed overexpression of WT1 mRNA (68.4%). The rates of WT1 mRNA expression were higher than what we observed. In their study, endothelial cells from blood capillaries, muscle cells, and myoepithelial cells in the sample tissues also expressed WT1 protein, and blood capillaries proliferated more in the tumor stroma than in intact mucosa [10]. According to the results of Mikami et al., the frequency of WT1 protein overexpression in OSCC tissue samples was 6.9%, and all of the cases with WT1 expression were well-differentiated. Similarly, in our study, the frequency of WT1 overexpression was 6.2%, and all of the cases with WT1 expression were well-differentiated.

Our results disagree with those of Oji et al., who reported that high WT1 expression levels were significantly correlated with poor histologic tumor differentiation and advanced tumor stage in head and neck SCC. However, the samples in our study had similar demographics as the study by Eshghyar et al., who found similar results [18].

Normal oral epithelium maintains its structure by a continuous renewal of cells, in which, cells produced by mitotic

division in the lower cell layers of the basal epithelium migrate to the surface to replace cells that have been shed. This phenomenon is also frequently seen in the cancer nests of well-differentiated OSCC samples, where the basal layer proliferates in this fashion. In this study, although WT1 was not expressed in the basal layer of normal epithelium, it was expressed in the basal layer of infiltrating and proliferating cancer nests of the same tissue specimen. This suggests that WT1 is important to the neoplastic proliferation of cancer cells. Amassing more data from OSCC cases displaying overexpression of WT1 is necessary to determine the epidemiologic correlations that exist between WT1 and OSCC. Based on observations of the morphological features of tissue specimens and the expression patterns of WT1, WT1 appears to play an important role in the pathogenesis of some types of OSCC, particularly in the proliferation of cancer cells [19].

Two separate phase I clinical studies were performed by Tsuboi et al. and Oka et al. using WT1 peptide-based cancer immunotherapies on patients with OSCC with high WT1. Both studies demonstrated a decrease in WT1 expression and were considered to be effective. Thus, our findings and this phase I clinical studies suggest that although the pathogenesis of OSCC is diverse, WT1 peptide-based immunotherapy could have a role as a new treatment option for OSCCs that have WT1 overexpression [20].

Conclusion

WT1 expression was reported in 6.2% of all studied cases in this survey. Additionally, the WT1-positive samples were welldifferentiated. However, the association of WT1 expression with the proliferation of malignant cells remains inconclusive. Collecting more data to examine the relationship between WT1 expression and any relevant clinicopathologic variables in oral SCC is essential.

Acknowledgment

This study has been approved as a student project at the Gingiva Research Center of Tabriz University of Medical Sciences and has been accepted by the Ethics Committee of the Tabriz University of Medical Sciences.

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