The Expression Of FHIT, P53 And Ki-67 In Bladder Transitional Cell Carcinoma And The Relationship Between Them

Objective:To observe the expression of fragile histidine triad protein (FHIT) in transitional cell carcinoma and normal mucosa of bladder and to elucidate the potential relationship between FHIT protein expression and clinicopathologic features (age, gender, smoking history, tumor stage and histologic grade) of bladder transitional cell carcinoma. To determine the relationship between the expression of FHIT and expression of P53, Ki-67 in bladder transitional cell carcinoma.Methods:Immunohistochemical staining for FHIT, P53, and Ki-67 was performed on paraffin embedded sections from 97 bladder transitional cell carcinomas and 18 normal mucosa from patients who had been treated with surgery. The results were compared with clinicopathologic features (age, gender, smoking history, tumor stage and histologic grade). The expression of P53, Ki-67 and their relationship with FHIT were analysed.Results:The expression of FHIT was mainly found in the cytoplasm of the tumor cells, and positive staining for FHIT was found in 45% (45/97) of the bladder transitional cell carcinoma tissue samples and 89%(16/18) of the normal mucosa specimens (P<0.05). There was no correlation between the expression of FHIT of the tumor samples and the clinicopathologic features (including age, gender, smoking history, tumor stage and histologic grade) of the patients (P>0.05). The P53 protein expression was generally detected in the nucleus of the cells, and its expression was observed in 51 of 97 (53%) bladder transitional cell carcinoma tissue samples and 2 of 18 normal mucosa specimens (11%). The positive percentage was higher in the tumor group than in the normal group (P<0.05). The positive percentage was shown no difference in different age, gender, and smoking habit groups (P>0.05). In the 31 cases of bladder transitional cell carcinomas of low histologic grade (G1),10 cases were positive for P53 staining (32%), as in the 66 cases of tumor specimens of high histologic grade (G2+G3),41 cases showed positive P53 staining (62%). The positive rate of P53 staining in the high grade tumors was higher than that in the low grade ones (P<0.05). Of the 82 cases of non-muscle invasive transitional cell carcinomas (TiS-T1),37 (45%) revealed positive staining for P53 protein. Of the 15 cases of muscle invasive tumors (T2-T4),14 revealed positive (93%). The staining rate of P53 in the muscle invasive tumors was higher than that of the non-muscle invasive tumors (P<0.05). The Ki-67 protein expression was generally detected in the nucleus of the cells, and its expression was observed in 70 of 97 (72%) bladder transitional cell carcinoma tissue samples and 3 of 18 normal mucosa specimens (17%). the positive percentage was higher in the tumor group than in the normal group (P<0.05). The positive percentage was shown no difference in different age, gender, and smoking habit groups (P>0.05). In the 31 cases of bladder transitional cell carcinomas of low histologic grade (G1),11 cases were positive for Ki-67 staining (35%), as in the 66 cases of tumor specimens of high histologic grade (G2+G3),59 cases showed positive Ki-67 staining (89%). The positive rate of Ki-67 staining in the high grade tumors was higher than that in the low grade ones (P<0.05). Of the 82 cases of non-muscle invasive transitional cell carcinomas (TiS-T1),56 (68%) revealed positive staining for Ki-67 protein. Of the 15 cases of muscle invasive tumors (T2-T4),14 revealed positive (93%). The staining rate of Ki-67 in the muscle invasive tumors was higher than that of the non-muscle invasive tumors (P<0.05). P53 expression was significantly correlated with Ki-67 expression (P<0.05, r=0.721), but the loss of FHIT protein was not correlated with the expression of P53 or Ki-67.Conclusions:The loss of FHIT protein was related to the incidence of bladder transitional cell carcinoma, but the level of FHIT protein was not associated with age, gender, smoking habit, clinical stage and histologic grade of the tumor. No significant correlation found between the expression of FHIT and P53, Ki-67 suggested that for fragile histidine triad, the pathway of tumourigenesis may be independent of P53 and of tumoural proliferation.