This report describes a case of odontogenic cyst with keratinization and dysplastic change of lining epithelium, which showed the manifestation of inflammatory radicular cyst, clinically. A 28-year-old man complained of dull pain in the right mandibular molar region. Radiographically a well-defined oval cystic lesion with non-vital teeth, a common finding in radicular cyst, was observed. Microscopically, the lining epithelium of the cyst demonstrated both keratinization and severe epithelial dysplasia. Atypical findings such as hyperchromatic nuclei, increase of N/C ratio and drop shaped rege ridge were observed in the lining epithelium. However, definite invasion into fibrous connective tissue was not found. Immunohistochemically, the dysplastic lining epithelium was highly positive for proliferative marker, Ki-67. Based on the dysplastic changes of lining epithelium, this periapical lesion would be considered to be signs of malignant change. From this case, we conclude that definitive diagnosis by microscopical examination should be made, even if the periapical lesion would be clinically considered as inflammatory radicular cyst.

Epithelial-mesenchymal transition (EMT) can play an important role in carcinogenesis of oral squamous cell carcinoma (OSCC). EMT is characterized by morphological and phenotypical change of epithelial cells into mesenchymal cells, and transcriptional repressor of E-cadherin, Snail is critical for EMT. In order to investigate the role of Snail and E-cadherin in OSCC, we analyzed the immunohistochemical pattern of Snail and E-cadherin in 18 OSCCs. The expression of Snail in the OSCC was increased whereas the expression of E-cadherin in the OSCC was decreased in comparison with those of normal oral mucosa, showing reverse correlation. Especially, the fibroblasts near the islands of OSCC showed the positivity of Snail, suggesting the reactive fibroblasts to the EMT of epithelial tumor cells. In metastatic squamous cell carcinoma in cervical lymph node, the positivity of Snail of tumor cells was higher than that of primary OSCC. We concluded that the increased Snail expression and the decreased E-cadherin expression were involved in the progression, invasion and metastasis of OSCC.

Wntsignaling is involved in the normal development and tumorigenesis via epithelial- mesenchymal transition (EMT). init iated by down-regul ation of E-cadherin by the transc ription factor Snail. Wnt signaling inhi bits Sna il phosph o rylation t hrough Axin2-dependent pathway that sustains nuclear accumul ation 0 1' Snail by driving CSK3ß nucleocytoplasmic export then consequently increases Snail protein levels and induces an EMT However. the roles of Wnt and Axin expression and their functional implication on Snail dependent EMT program a re not clear du ring the multistep carcinogenic process. We examined that canonical Wnt signaling engagingmul t istep carcinogenic process of uterine cervical cancer through Wnt-Axin2-Snail axis. In nonnal cervi cal mucosa, Wntl. Wnt3a. and Axin2 mRNA expression were locali zed in basal cell layer suggesting that canonical Wnt is required for maintenance of self-renewal program of cervica l epi theli al cells. With progression to cervical int r aepithelial neoplasia (CIN) and carcinoma. Wntl, Wnt3a‘ Axin2, and Snail expression were gradually increased in patient samples suggesting that canonical Wnt pathway is involved in earl y step of carcinogenesis in uterine cervix. LRP6 and Axin2 transfected cells showed the highly increased nuclear Snai l resul ted from dec reased level 0 1' nu clear GSK3ß , indicating that LRP6- Axin2 serves to stabili ze Sna il protein levels and susLains iLs nllclear acc llrnulation by driv ing GSK3ß . RNA interference of Axin2 and Snail on SiHa cells relieved E-cadherin proximal promotel‘ activity and block the in 띠 vo chorioalantoic membra ne ln VaSlOn These results suggest the canon ical Wnt signa ling regul ating Axin2-GSK3ß compartmentalization may important for stabi li zation of E- cad herin repressor Snail during the multistep carcinogen ic process of uteri ne cervix. It may lead to not only tracing the proper biomarker 0 [' ca ncer progression‘ but a lso the development oJ new targets for therapeutic intervention in cancer