| IntroductionEndometrial carcinoma is one of the most common malignacy affecting adult women world — wide. To know the mechanism of the genesis and development of endometrial carcinoma is very important for diagnosis and estimate the prognosis of this disease, as well as for searching a new target for the treatment of endometrial carcinoma. People are searching for a new gene all these years that may be changed in the early stage of the tumor in structure and function. Fragile histi-dine trial gene (FHIT) may be this kind of gene. The FHIT gene was recently described as a candidate tumor suppressor gene implicated in the development of various tumors and cell lines derivated from cancers, including esophageal, gastric ,lung, head and neck, and so on. Proliferation cell nuclear antigen ( PCNA) is an indicator of cells proliferous state. We detected the expression of Fhit ptotein and PCNA in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma to know their association with the clinicopathologi-cal as well as to explore their function in the genesis and development of this kind of cancer.ObjectiveTo define the expression of fhit protein and PCNA in normal endometrium, atypical hyperplasia of endometrium and endometrial adenocarcinoma and the association with the clinicopathological features.MethodsThe expression of fhit protein and PCNA was detected by immuohistochem-istry in histological normal endometrium for 20 cases , endometrial adenocarci-noma for 57 cases, and atypical hyperplasia of endometrium for 9cases.The standard of Fhit protein expression: Cells filled with yellow or brown granules in cytoplasm were considered as positive immunostained cells. Both the extent and intensity of immunostaining were considered when Fhit protein expression of a section was scored according to Zhao Po. The extent of positivity was scored as follows; 0, <0% ; 1, ≤10% ; 2, 11 -50% ; 3, 51 -75% ; and 4, >75%. The intensity was scored as follows; 0, negative; 1, weak yellow; 2, brown; and 3 ,. deep brown. The final score was obtained by multiplying the extent of positivity and intensity scores, Scores ≥2 were defined as positivity.The standard of PCNA expression; PCNA positively immunostained cells were filled with brown granules in nuclei. The positive cells were observed and calculated under a light microscope in 5 high power fields ( 400). Proliferation index (PI) expressed as the ratio of positively stained cells to total cells of the fields, If PI ≥50% ,we called it HI,and < 50% ,LI.Results1. The expression of fhit protein in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma;The positive percent of fhit protein in normal endometrium, atypical hyperplasia endometrium and endometrial carcinoma was 20/20 ( 100% ) , 6/9 and 31/57 (54. 39% ) respectively. The result was no association between atypical hyperplasia endometrium and endometrial adenocarcinoma,P =0. 490,and there was significant statistical relation between normal endometrium and endometrial adenocarcinoma,P =0. 0002,as well as normal endometrium and atypical hyperplasia endometrium,P =0. 023.2. Association between the expression of. fhit and clinicopathological fea-ture:We examined fhit protein expression in 57 endometrial carcinoma cases, and found in 31 of 57 (54. 39% ) with positive expression. Association of positive expression of fhit and histological grade was evaluated: The positive fhit expression was observed in 15/20 (75%) G1 endometrial adenocarcinoma, and 11/22 (50% ) G2 endometrial adenocarcinoma,but only 5/15(33. 33% ) G3 endometrial adenocarcinoma,indicating significant association between positive expression of fhit protein and the histological grade of the tumor. The result showed us that there was no statistical association between G1 endometrial adenocarcinoma and G2 endometrial adenocarcinoma, P =0.096,and no statistical association between G2 endometrial adenocarcinoma and G3 endometrial adenocarcinoma either, P = 0. 096. there was significant statistical relation between normal endometrium and endometrial adenocarcinoma, P = 0. 0002.We also found the relation between the positive expression of fhit protein and the advanced surgical stage: The positive fhit expression was observed in 26/ 41(63.41% ) in the cases at stage I ~ II, while it was 6/15(31. 25% ) in the cases at stage III - IV. The result suggested that there was significant statistical relation between the positive expression of fhit protein and the advanced surgical stage, P =0.028.3. The expression of PCNA in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma:The higher proliferation rate in normal endometrium, atypical hyperplasia endometrium and endometrial carcinoma was 2/20(10% ) ,1/9 and 31/57(54. 39% ) respectively. The result was no association between atypical hyperplasia endometrium and normal endometrium, P = 1. 000. , and there was significant statistical relation between normal endometrium and endometrial adenocarcinoma, P = 0.0005. ,as well as endometrial adenocarcinoma and atypical hyperplasia endometrium, P = 0. 040.4. Association between the expression of PCNA and clinicopathological feature;We examined PCNA expression in 57 endometrial carcinoma cases, andfound in 31 of 57 (54. 39% ) with higher proliferation rate. Association of higher proliferation rate and histological grade was evaluated: The higher proliferation rate was observed in 6/20 (30% ) G1 endometrial adenocarcinoma, and 13/22 (59. 09% ) G2 endometrial adenocarcinoma, but only 12/15(80% ) G3 endometrial adenocarcinoma, indicating significant association between higher proliferation rate and the histological grade of the tumor. The result showed us that there was no statistical association between G1 endometrial adenocarcinoma and G2 endometrial adenocarcinoma, P= 0.059,and no statistical association between G2 endometrial adenocarcinoma and G3 endometrial adenocarcinoma either, P =0. 286. there was significant statistical relation between normal endometrium and endometrial adenocarcinoma, P = 0.006.5. Abnormal PCNA expression was associated with high histological grade. The higher proliferation rate of these cases with positive expression of fhit was 36. 67% , while it was 79.92% of these with negative fhit expression,shown significant association between these two factors. The result showed us that there was no statistical association between G1 endometrial adenocarcinoma and G2 endometrial adenocarcinoma, P= 0.096,and no statistical association between G2 endometrial adenocarcinoma and G3 endometrial adenocarcinoma either, P =0. 096. there was significant statistical relation between normal endometrium and endometrial adenocarcinoma,P =0.002.Conclusion1. The abnormal expression of fhit protein and PCNA was important genetic events associated with the genesis and development of endometrial carcinoma. Loss of Fhit expression was associated with high malignant potential, including advanced surgical stage and high histological grade. Abnormal PCNA expression was associated with high histological grade.2. Our observations suggested that Fhit could interact with PCNA. Abnormal expression of PCNA may be result from the absent or reduce expression of fhit protein.3 Fhit protein may be a new target for the treatment of endometrial carcino-...
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