Desmoglein-3/γ-catenin and E-cadherin/ß-catenin differential expression in oral leukoplakia and squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to investigate gene/protein expression alterations of intercellular connections' components in oral leukoplakia (OLs) and squamous-cell carcinoma (OSCCs). MATERIALS AND METHODS: Expression of desmogleins-2,3 (Dsg2/Dsg3), E-cadherin, and their cytoplasmic ligand, ß/γ-catenins were quantitatively assessed in HSC-3 cells growing as monolayer cultures (ML)/multicellular aggregates (MCAs), using RT-PCR/Western blot, whereas their localization was detected by immunofluorescence. Furthermore, their expression was semi-quantitatively investigated in tissues from 25 OLs/25 OSCCs, using automated immunohistochemistry. RESULTS: The steady-state levels of Dsg3 RNA transcripts increased as HSC-3 cells enter their exponential phase of growth, before a dramatic decrease to be observed as cells reached their plateau phase especially in MCAs. Upon the same period of time, Dsg2 levels have been increased. The expression of γ-catenin but not that of ß-catenin was increased after 48 h in both MLs and MCAs. In clinical samples, Dsg3, Ε-cadherin, ß/γ-catenin down-regulation was observed to be associated with the grade of OLs-dysplasia and OSCCs. Importantly, a membrane-to-cytoplasmic switch of expression and strong perinuclear aggregation of Dsg3/γ-catenin was seen in both HSC-3 cells and OLs/OSCCs. CONCLUSIONS: The altered expression of Dsg3/γ-catenin and E-cadherin/ß-catenin, in vitro and in ODs/OSCC imply their involvement in growth regulation and phenotype of dysplastic/malignant oral epithelial cells, contributing to the better understanding of epithelial dysplasia and OSCCs. CLINICAL RELEVANCE: The observed alterations of their expression suggest a role of Dsg3 and γ-catenin (additionally to E-cadherin/ß-catenin) as biomarkers of malignant transformation risk of oral dysplasia and the biological behavior (aggressiveness) of oral cancer, respectively.

Can cetuximab affect paraneoplastic myopathy?

Cetuximab given concurrently with chemotherapy has shown survival benefit for patients with metastatic colon cancer. We report a case of a patient with metastatic colon cancer who developed paraneoplastic necrotizing myopathy that possibly responded to cetuximab despite lack of improvement of the underlying cancer.

Immunocytological and preliminary immunohistochemical studies of prothymosin alpha, a human cancer-associated polypeptide, with a well-characterized polyclonal antibody.

Prothymosin alpha (ProTalpha) is a nuclear polypeptide of great biological and, possibly clinical, importance, because its expression levels have been associated with early diagnosis/prognosis of human cancer. It is therefore interesting to raise easily available and cost-effective antibodies that would be applied to develop reliable ProTalpha immunodiagnostics. In this study, New Zealand white rabbits and laying hens were parallel immunized against intact ProTalpha or the synthetic fragments ProTalpha[1-28], ProTalpha[87-109], and ProTalpha[101-109], all conjugated to keyhole limpet hemocyanin (KLH). The corresponding antibodies G and Y were immunochemically evaluated in parallel with ELISA and Western blot systems and applied to fluorescence immunocytology experiments using various cancer cell lines and normal cells. The antibody G raised against ProTalpha[101-109]/KLH had excellent functional characteristics in the Western blot and immunocytology experiments, where the fluorescent signal was almost exclusively shown in the cell nucleus independently of the cells assayed. The above antibody has been applied to preliminary IHC staining of human cancer prostate tissues, leading to a high percentage of clearly and intensively stained nuclei in the adenocarcinoma tissue; this antibody can be further used in cancer tissue immunostaining and in research concerning the role of ProTalpha in tumorigenesis.