The molecular mechanisms of the carcinogenesis of oral squamous cell carcinomas (OSCCs) are highly variable and result in different features of tumor progression, i.e., local tissue destruction and metastasis to regional lymph nodes. A case of OSCC arising from proliferative verrucous leukoplakia (PVL) was analyzed for its protein expression profile by immunoprecipitation (IP) – high performance liquid chromatography (IP-HPLC) by using 72 antisera and comparing results with those of KB cells. OSCC arising from PVL showed stronger expressions of proteins associated with cell proliferation (MPM2, PCNA, eiF5A, DHS, DOHH), cell survival (pAKT, MDM2, survivin), matrix proteolysis (elaffin), tumor suppression (p16, p21, PTCH1), the WNT/β-catenin pathway (SHH, WNT1, APC, β-catenin, snail), proinflammation (TNFα), angiogenesis (HIF, CMG2, vWF), and cellular protection (HSP-70, FAK, caveolin) and of oncoproteins (STAT3, 14-3-3, K-RAS, PUMA, PIM1) and growth factors (EGFR, bFGF) than KB cells. On the other hand, KB cells showed stronger expressions of proteins associated with apoptosis (caspase-3, caspase-8, caspase-9, PARP, FAS, FASL, TGase-1, BCL2, BAD, BID, BAK, FLIP), matrix proteolysis (MMP-2, MMP-9), transcription signaling (NFkB, p38, E2F-1, HO-1), and tumor suppression (p53, RB1, PTEN) and of oncoproteins (DMBT1, CEA) and growth factor (TGF-β1, c-erbB2, VEGF) than OSCC arising from PVL. These data indicate the cells of OSCC arising from PVL are more resistant and more robust than KB cells. Furthermore, they suggest the oncogenic signalings of OSCC arising from PVL play important roles in the aggressive growth and rapid tumor metastasis to regional lymph nodes

Development of squamous cell carcinoma around dental implants is an uncommon clinical manifestation with only a few cases described in the literature. Recently, we observed primary squamous cell carcinoma that developed from leukoplakia around dental implants. We report this case to emphasize the importance of careful oral examination, for implant surgery has to be preceded by thorough evaluation of oral mucosal conditions.

Oral erythroleukoplakia is characterized by severe dyskeratosis intermingled with multifocal erosive spots on the buccal mucosa, dorsal tongue, and lower lip, etc. A case of oral erythroleukoplakia was diagnosed among 83 cases of common oral leukoplakia since 1997. The pathological examination showed the typical features of leukoplakia with severe epithelial dysplasia, exhibiting dyskeratosis, acanthosis, and basal hyperplasia. The oral erythroleukoplakia was explored in comparison with a representative common oral leukoplakia by the immunohistochemical method using PCNA, β-catenin, EGFR, p53, TNFα, pAKT, and STAT3. Oral erythroleukoplakia showed strong positive reaction of PCNA, p53, EGFR, TNFα, pAKT1 and STAT3 in its spinous layer cells and these reactions were reduced in its basal layer cells, while common oral leukoplakia showed diffusely weak reaction of those proteins. Particularly, β-catenin was positive in the nuclei of some basal and spinous layer cells of oral erythroleukoplakia contrast to the common oral leukoplakia. These findings indicated that the present oral erythroleukoplakia was proliferative with the activation of β-catenin pathway, revealed the dysplastic changes of epithelium by the overexpression of EGFR, p53, and pAKT, and also produced inflammatory reaction through the activation of cytokine-dependent signalings of TNFα and STAT3. These data indicated that the present oral erythroleukoplakia might undergo the early stage of multi-step carcinogenesis via the overexpression of different oncoproteins, especially β-catenine, p53, pAKT, and STAT3.

to malignant transformation. Oral leukoplakia is a common premalignant lesion in oral mucosa and the incidence of cancer progression into SCC has been reported to be 0~43%. The genetic alterations of oncogenes, tumor suppressor genes and DNA repair genes occur during carcinogenesis. In order to evaluate the role of epithelial cells in the early stage of carcinogenesis, we analyzed the alterations of genetic heterogeneity in epithelial cells of oral leukoplakia samples, using Laser capture microdissection(LCM). The incidence rate of microsatellite instability(MSI) and loss of heterozygosity(LOH) were analysed from the DNA of epithelial cells from 16 leukoplakia samples using adjacent fibroblasts as a normal control. In this study, LOH was found in epithelial cells of all 16 cases of leukoplakias while MSI has been observed in 3 cases. Interestingly, the fibroblasts showed LOH and MSI in some cases, which was confirmed by DNA sequencing. Taken together, this study showed that leukoplakia has multiple genetic alterations in fibroblasts as well as in epithelial cells, suggesting that interaction between epithelial cells and fibroblasts might be involved in the early step of carcinogenesis.