The Expression And Significance Of FHIT, Livin And Smac In Oral Squamous Cell Carcinoma

Objective: Oral squamous cell carcinoma (OSCC) is one of the most common oral cancers. Over 80% of oral cancers are oral squamous cell carcinomas. With its high occurrence rate and low survival rate, OSCC is extremely harmful to human health. The occurrence and development of OSCC covers many stages and involves the change of various cell genetic materials. The loss of FHIT expression takes place at an early stage in the development of OSCC. Studies show that FHIT as the upstream gene on the pathway of PI3K/Akt regulates the signals of apoptosis meditated by PI3K/Akt. Livin is the most powerful apoptosis inhibitory factor in the IAPs family. Livin regulated by the cell signal transduction pathway of PI3K/Akt has a direct effect on Caspase-3 and Caspase-7. In normal physiological situation, FHIT inhibits the pathway of PI3K/Akt and therefore inhibits the expression of Livin. In some pathological cases, FHIT shows a decrease or loss in the process of expression and weakens its regulation of the pathway of PI3K/Akt and conversely, Livin shows an increase in expression and thus inhibits apoptosis. Meanwhile FHIT may regulate cell cycles through ubiquitin conjugated enzyme. Besides , the high expression of exogenous FHIT may cause mitochondria to change. Smac, discharged to cytoplasm by mitochondria, is an important apoptosis regulatory factor. It may combine with all the IAPs that have been discovered and cause them to lose their activity to inhibit caspase. At the same time, Livin, as E3 ubiquitin ligases, may dissolve Smac. This study, by means of immunohistochemical staining method, aims to test the expression of FHIT, Livin and Smac in OSCC, and to explore their functions and corelation in the occurrence and development of OSCC.Materials and Methods: 38 specimens OSCC embedded in paraffine, 17 oral precancerous lesion specimens(including 7 oral leukoplakia specimens, 8 oral lichen planus specimens and 2 atypical hyperplasia specimens) and 9 hyperplasia specimens were chosen. Immunohistochemi- cal (SP) was used to detect FHIT, Livin and Smac. The results were statis- tically analyzed by SPSS 11.5 software. K Independent Test and 2 Indepen- dent Test were used to compare the expressions of FHIT, Livin and Smac in OSCC as well as their correlation in the occurrence and development of OSCC by Spearman. There was a statistical significance with P<0.05.Results: The positive rates of FHIT in normal tissues, precancerous lesions, OSCC and lymph node metastases are 100.0%,100.0%,76.3%,50.0% respectively. There are marked differences in expression between normal tissues group and OSCC group, between normal tissues group and lymph node metastases group ,between precancerous lesions group and OSCC group, between precancerous lesions group and lymph node metastases group. The positive rates of Livin in normal tissues, precancerous lesions, OSCC and lymph node metastases are 55.6%,58.9%,100.0%,100.0% respec- tively. There are marked differences in expression between normal tissues group and OSCC group, between normal tissues group and lymph node metastases group ,between precancerous lesions group and OSCC group, between precancerous lesions group and lymph node metastases group, between metastasis group and non- metastasis group in OSCC. The positive rates of Smac in normal tissues, precancerous lesions, OSCC and lymph node metastases are 100.0%,100.0%,76.3%,50.0% respectively. There are marked differences in expression between the combination of normal tissues group and precancerous lesions group and OSCC group.Conclusion: 1. The loss of FHIT or Smac is likely to be an early occurrence in the development of OSCC. 2. The abnormal expression of Livin might exert influence on the development of OSCC. 3. FHIT , Livin and Smac interact in OSCC.