ABSTRACT
OBJECTIVE: To investigate the clinical significance of vimentin expression at early and late events of tobacco/areca nut-associated oral tumorigenesis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was carried out on paraffin-embedded tissues of oral mucosa normal (n = 10), inflammatory lesions (n = 19), leukoplakia (n = 52), submucous fibrosis (n = 71) and tumours/cut margins (n = 227 each), using anti-vimentin antibody, and the expression profile was correlated with patients' clinical parameters. Immunofluorescence, Western blot and RT-PCR analysis were also carried out wherever adequate and fresh tissues were available. RESULTS: Aberrant vimentin expression was seen in hyperplastic, dysplastic and fibrotic tissues, which showed statistically significant correlation with the histopathological grade of dysplasia (P = 0.001) and fibrosis (P = 0.009). Vimentin expression also showed statistically significant correlation with tumour size (P = 0.048), clinical stage (P = 0.013), regional lymph node metastases (P = 0.001), local recurrence (P = 0.001) and survival (P = 0.021) of patients with oral squamous cell carcinoma (OSCC). Its expression in invasive fronts statistically correlated with development of nodal metastasis and local recurrence. CONCLUSIONS: Our results suggest possible role of vimentin in early events of tobacco/areca nut-associated oral tumorigenesis, which may prove useful to predict the malignant potential of high-risk oral lesions. Further, association between vimentin expression in invasive fronts and aggressive phenotype of tumours may help clinicians to choose the appropriate treatment modality for OSCC management.
Subject(s)
Mouth Neoplasms/chemistry , Precancerous Conditions/chemistry , Vimentin/analysis , Adolescent , Adult , Aged , Blotting, Western , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/pathology , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Mucosa/chemistry , Mouth Neoplasms/pathology , Precancerous Conditions/pathology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Recently, we have demonstrated that omega-6 fatty acid linoleic acid (LA) in presence of estradiol (E2) enhances proliferation and anchorage independent growth with down regulation of BRCA1 mRNA expression in MCF-7 cell line. Since omega-3 fatty acid (docosahexanoic acid, DHA) is known to block the promoting effect of omega-6 polyunsaturated fatty acid (LA), we wanted to see whether addition of DHA can inhibit the growth of MCF-7 cells which are exposed to LA + E2 and any alteration of BRCA1 mRNA expression could be seen in DHA treated culture. Experiments on MCF-7 cells with DHA revealed both decrease in proliferation and anchorage independency as compared to controls; while no change of BRCA1 mRNA expression was observed. Further, when DHA was administered to cells along with LA + E2, no change in BRCA1 expression was observed, however, a marked decrease in proliferation and soft agar colony formation was evident, indicating inhibition of MCF-7 cells following DHA treatment. Flow cytometric analysis showed that DHA treated cells either alone or in combination with LA + E2 induced marked G1/S and G2/M arrest of the cells, suggesting the inhibitory effect of DHA at this phase of cell cycle. However, neither typical DNA ladder nor fragmented nuclei or apoptotic bodies were observed, ruling out presence of apoptosis following DHA treatment.
