Wnt Signaling as a Possible Promoting Factor of Cell Differentiation in Pleomorphic Adenomas

Abstract

There are well known that Wnt signaling was some roles of cell differentiation at the development tissues, especially the oral and maxillofacial regions of some developmental stages. Therefore, to determine Wnt signaling in the pleomorphic adenoma tissues, we examined. The expression of Wnt1 and β-catenin as well as the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30 cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost all tumor cells. The peripheral columnar cells in squamous metaplasia and small cuboidal cells in duct-like structures were strongly positive to Wnt1. Although β-catenin was clearly localized on the cell membrane of tumor cells, nuclear translocation was observed in small cuboidal cells and in some basaloid cells. The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests and small peripheral columnar cells forming duct-like structures. Moreover, among the three currently known Wnt pathways, β-catenin is the suggested pathway working during cell differentiation. Furthermore, peripheral columnar cells in solid tumor nests and in squamous metaplasia are governed by another Wnt pathway other than β-catenin. Therefore, Wnt signaling through β-catenin pathway may be involved in the 'mixed' differentiation characteristic of pleomorphic adenoma although another pathway may also be possibly working in other parts of the tumor tissue.

Notch as a Possible Cell Differentiation Factor in Pleomorphic Adenomas

“…In the study by Okuda et al, small cuboidal cells forming ductal structure expressed Wnt and the expression was also confirmed in the basal cells surrounding those cells undergoing squamous metaplasia. The results coincided with our present study implicating the function of Notch in the same sites causing cell differentiation 2 .…”

“…Comparing the results of our study with previous reports, from the partial CK7 expression and substantial Notch expression in ductal epithelial cells as well as the Notch expression in solid tumor nests, it can be inferred that Notch is involved in cell differentiation 2 , 22 . CK13 expression was observed in cells undergoing squamous metaplasia and Notch expression was seen in the nucleus of basal and squamous cells 23 .…”

“…The results showed that tumor cells in ductal structure and in solid tumor nests expressed Wnt. It was inferred that β-catenin pathway was involved in cell differentiation indicated by Wnt expressions in cells undergoing squamous metaplasia 2 . For this reason, we believed that Notch would have a role in tumor cell differentiation considering its association with other tumors 7 , 8 .…”

“…A total of 30 cases of PA based on WHO classification were used in this experiment. The specimens used in this study were the same as those used by Okuda et al 2 , described in Table 1 .…”

“…Various cell types can be seen in the tumor indicating a high occurrence of cell differentiation. Okuda et al performed immunohistochemistry on PA to determine the role of Wnt in cell differentiation 2 . The results suggested that Wnt is involved in cell differentiation in PA.…”