β-Catenin Is Expressed Aberrantly in Tumors Expressing Shadow Cells: Pilomatricoma, Craniopharyngioma, and Calcifying Odontogenic Cyst

Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, PO Box 100275, Gainesville, FL 32610, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 12/2003; 120(5):732-6. DOI: 10.1309/EALE-G7LD-6W71-67PX
Source: PubMed


We studied the beta-catenin immunohistochemical profile in tumors expressing shadow cells: pilomatricoma, 10 cases; calcifying odontogenic cyst, 6 cases; and craniopharyngioma, 9 cases. There was strong membranous, cytoplasmic, and nuclear staining of the immature basaloid cells in all of these tumors. Shadow cells were negative in all tumors. It has been documented that rising levels of free beta-catenin drive the formation of complexes with T-cell factor/lymphoid enhancer factor (TCF-Lef) and up-regulate the wingless-Wnt cell-cell signals. The end result is an abnormality of beta-catenin degradation and, thus, a buildup of free beta-catenin in the cytoplasm and/or nucleus, resulting in the stimulation of cellular proliferation and/or inhibition of cell death. beta-Catenin seems to have an important role in the oncogenesis of these tumors. The similar pattern of keratinization in these tumors and the similar pattern of beta-catenin immunoreactivity in the cytoplasm and the nucleus are important findings. It seems that the activation of a common cellular pathway, namely Wnt-beta-catenin-TCF-Lef, has a role in the pathogenesis of these tumors. The latter could be related to their shared method of keratinization or shared dysfunction of the cellular adhesion complex leading to tumorigenesis.

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    • "In the normal state, -catenin binds to the cell membrane as a part of the membranebound cadherin-catenin complex (Hassanein et al., 2003). The association of the cytoplasmic domain of cadherin with the actin cytoskeleton via catenin is critical for cell-cell adhesion. "
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    ABSTRACT: Odontogenic keratocyst is now designated by the World Health Organization as a keratocystic odontogenic tumor (KCOT). According to recent reports Wnt pathway and ß-catenin are involved in the pathogenesis of the majority of odontogenic and neoplastic lesions. The aim of this study was to evaluate the expression of ß-catenin in KCOT and compare it with those of dentigerous cyst and ameloblastoma. Expression of ß-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 57 formalin-fixed paraffin-embedded samples of KCOT, dentigerous cyst and ameloblastoma (19 samples in each group). The expression of - catenin protein was observed separately in the membrane, cytoplasm and nucleus of epithelial cells. Percentages of expression of membranous, cytoplasmic, and nuclear ß-catenin were 68.4%, 89.5% and 5.3% for KCOT; 78.9%, 100%, and 26.3% for ameloblastoma and 42.1%, 84.2%, and 5.3% for dentigerous cyst, respectively. The expression of membranous ß-catenin in the dentigerous cyst was significantly lower than that in KCOT and ameloblastoma (P<0.05). In other cases, there were no significant statistical differences between the three groups. Membranous expression of ß-catenin might be useful in differentiation of KCOT and ameloblastoma from dentigerous cyst. However, intracellular accumulation of this protein cannot be used to prove the neoplastic nature of KCOT versus dentigerous cyst. Moreover, considering the intracellular accumulation of ß-catenin in most cases in all the three lesions, it seems that ß-catenin changes might play a role in development of odontogenic epithelium in this lesion through deregulation of cell cycle.
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    • "Furthermore in odontogenic tumors like ameloblastoma 21, calcifying cystic odontogenic tumor 22-25, odontoma and calcifying epithelioma, Wnt signaling through β-catenin pathway is involved in ghost cells 26. Although the functions of Wnt signaling in salivary gland tumors especially on malignant tumors have also been done in cell cultures, likewise, we thought that Wnt signaling is involved in malignant salivary gland tumors 27. "
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    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.
    International journal of medical sciences 07/2014; 11(9):971-8. DOI:10.7150/ijms.9453 · 2.00 Impact Factor
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    • "They are typical for pilomatrixoma and other cutaneous tumors with follicular differentiation, and it was suggested that they represent faulty attempts at differentiation toward hair [1, 2]. Shadow cell differentiation (SCD) was, however, found also in noncutaneous lesions, such as craniopharyngioma [3], odontogenic cyst [3], gonadal teratomas [4–6], and in some visceral carcinomas, including uterine and ovarian endometrioid carcinomas [7–14]. To our knowledge, SCD was not reported in high-grade basaloid carcinoma of the ovary [15], before. "
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    ABSTRACT: So-called shadow cell differentiation (SCD) is typical for pilomatrixoma and other skin lesions with follicular differentiation, but it was rarely described also in some visceral carcinomas. We report a case of ovarian basaloid carcinoma with SCD. The tumor presented as a 14 cm ovarian mass in a 45-year-old woman, and therefore the adnexectomy and hysterectomy were performed. The tumor was of high stage. Multiple metastases were found in the liver, retroperitoneal and mediastinal lymph nodes, and the lung. Histologically, the tumor showed a pattern of high-grade basaloid carcinoma with numerous shadow cells. Extensive histologic examination did not reveal any glandular or preexisting teratoma component. Immunohistochemically, the tumor expressed markers of squamous cell differentiation, such as p63, cytokeratin 5/6, and high-molecular-weight keratin. Cytokeratin 7 and CA125 were positive in scattered cells of the lesion. Estrogen and progesterone receptor, vimentin, and p53 were negative. Beta-catenin showed nuclear and cytoplasmic positivity, indicating possible tumor proliferation/differentiation via Wnt signaling pathway. To our knowledge, SCD in basaloid carcinoma of the ovary was not described before. In addition to the description of the case, we review the literature on SCD in visceral carcinomas.
    02/2014; 2014:391947. DOI:10.1155/2014/391947
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