Loss of cytokeratin and gain of vimentin expression are indicators of biologically aggressive breast carcinoma.

Loss of cytokeratin and gain of vimentin expression are indicators of biologically aggressive breast carcinoma.

Aim: Activating mutations of FLT3 are commonly found in AML patients and reported to be associated with poor clinical outcome. We aimed to evaluate the incidence of FLT3 mutations along with FLT3 mRNA and CD135 protein expression in AML patients of western India and their role in prognosis of disease.Method: Analysis for the detection of FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out in total 174 de novo patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and aplastic anemia using PCR and RT-PCR methods. FLT3 protein was quantified by flow cytometry on leukemic blasts. Results:The incidence of FLT3 ITD, FLT3 TKD mutations and CD135 protein expression was found to be 19%, 7% and 62% respectively in AML patients. In MDS, only FLT3 ITD mutation and CD135 protein over expression could be analyzed, incidence of which was 22% and 60%. In aplastic anemia, FLT3 mutations, FLT3 mRNA and protein over expression were not detected. FLT3 mutations as well as FLT3 mRNA and protein over expression were prominently noted in AML subtypes associated with myelo-monocytic lineage. CD135 protein over expression was significantly associated with reduced Disease Free Survival (DFS) whereas WBC and blasts emerged as poor prognostic factors with respect to Disease Free Survival (DFS) and Overall Survival (OS) respectively in multivariate analysis. Conclusion:Our data suggest that CD135 receptor protein over expression is a potential prognostic marker as well as molecular target for FLT3 inhibitors in AML patients.

The present study evaluated 5 of the 8 main TP53 mutation hot spots in cancer by restriction site mutation analysis and compared the results with p53 protein expression in patients with cancer of the tongue. Tumor samples from 49 patients with tongue cancer were screened for TP53 mutations in exons 5 through 8 by PCR restriction site mutation analysis and for p53 protein expression by immunohistochemistry using the DO-7 antibody. Nuclear accumulation of p53 protein was seen in 22% (11/49) of the tumors, whereas none of the patients exhibited TP53 mutations in exons 5 through 8. The observed data suggest that TP53 mutations alone are not responsible for abnormal accumulation of p53 protein in tobaccochewing-mediated tongue carcinogenesis.

BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype. Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis.