Fhit, Bcl-2and Bax Expression In Cervical Cancer And Its Clinical Significance

Purpose: Through testing in normal cervical tissue, cervical intraepithelial neoplasia(CIN) and in different stages and different pathological types of cervical carcinoma, theexpression of Fhit protein in cervical cancer and the expression of Bcl-2and Bax, analysis ofFhit protein expression and cervical cancer pathological types, clinical stage, histologicaldifferentiation degree, with no lymph node metastasis in relation to each other, and toinvestigate the effect of Fhit and apoptosis related factors in Bcl-2/Bax, Fhit genes maybecome cervical cancer tumor suppressor genes and the new target of gene therapy to lay thefoundation.Method:In100specimens are from the Jilin University China-Japan FriendshipHospital in2010February to2011October during the obstetrics and gynecology outpatientand hospitalization in patients with cervical tissue paraffin block.Preoperative were not takenfor treatment.We group them as follows:(1)The normal control group:Due to a cervicallesions of hysterectomy,The postoperative pathology confirmed as normal cervical tissue ofpatients with,a total of16cases, age34-56between years, mean age42.8years;(2)CINgroup:In the clinic of concurrent cervical cone excision or due to cervical lesions ofhysterectomy, postoperative pathology confirmed that CIN,a total of23cases,the CIN I-IIgroup:13cases,the CIN III group:10cases, age of27-59, mean age39.0years.(3)Cervicalcancer group:61cases of cervical cancer, at the age of29-68, mean age44.7years.Accordingto the pathological types:46cases of squamous cell carcinoma, adenocarcinoma in15cases,both in the preoperative cervical biopsy pathology.According to clinical stage (in referenceto the2009FIGO staging): I patients in41cases, IIA patients in20cases, were treated withradical hysterectomy and pelvic lymphadenectomy.According to the lymph node metastasis:associated with lymph node metastasis in14cases, no lymph node metastasis in47cases.According to the pathological grading: low differentiation in22cases,23cases ofdifferentiation, high differentiation in16cases.The average age of three groups had nosignificant differences (P <0.05), with statistical significance.All specimens were fixed by10%formaldehyde solution fixed24hours again, paraffin embedding, made of4micronssections, each specimens cut4,first HE staining, the other for immunohistochemistry.Innormal cervical tissue and CIN as positive control,using0.01mol/L PBS instead of as anegative control.The experimental results of the judging standard of Fhit protein in epithelial cells of the cytoplasmic expression, dyed brown for the positive expression.According toHao, the semiquantitative scoring criteria to define:Fhit protein to the cytoplasm appearbrown granules for positive cells, in accordance with the staining intensity and scope ofscore. The final score for the expression of Fhit protein staining and staining intensity ofproduct, the positive expression of4-9is that the normal expression;1-3points is divided intoFhit protein negative abnormal expression (reduced expression or lossed ofexpression).Bcl-2, Bax protein in cytoplasmic staining, a few nuclear staining.Cytoplasmicor nuclear membrane with brown as positive expression, high magnification, counting5viewthe number of positive cells and the total cell number, and percentage of positive cells,set thenumber of positive cells＞10%is positive, or negative.All biopsies by pathologists blindeddetermination.Application of SPSS16.0software to deal with the data, count data using X2test correlation analysis.P <0.05indicates that the difference was statistically significant.Spearman rank correlation nonparametric statistics analyzed.Result:(1)In16cases of normal cervical tissues protein Fhit negative expression rate of0;in13cases of CIN I-II Fhit in tissue protein negative expression rate of23.08%;in10casesof CIN III Fhit in tissue protein negative expression rate of40.00%;in61patients withcervical carcinoma Fhit protein negative expression rate of72.13%.Fhit protein negativeexpression rate of normal cervical tissueâ†'CIN I-IIâ†'CIN IIIâ†'cervical cancer wasincreased.Fhit proteins in CIN in I-II group was significantly higher than that of negativeexpression in normal cervical tissue, two groups had significant difference (P <0.05).CIN IIIgroup Fhit protein negative expression rates of CIN in I-II group, but the two groups had nostatistical significance (P>0.05).Fhit protein in cervical carcinoma in the group of negativeexpression was significantly higher than that of CIN group III, two groups had significantdifference (P <0.05).Show abnormal expression of Fhit protein (low expression or noexpression) in cervical carcinogenesis, development.(2)61cases of cervical cancer, theexpression rate of Fhit protein negative, Bcl-2and Bax positive rates were associated withcervical cancer clinical staging, histological differentiation and lymph node metastasis.Incervical cancer,41patients with I and20patients with stage IIA,Fhit protein negativeexpression rates were63.41%,90%.The positive expression rates of Bcl-2protein were53.66%,90%.The positive expression rates of Bax protein were58.54%,25%.All groupshave significant difference(P <0.05).According to cervical cancer histopathologicaldifferentiation can be divided into groups of high differentiation, differentiation and lowdifferentiation group.Fhit protein negative expression rates were37.50%,73.91%,95.45%.The positive expression rates of Bcl-2protein were18.75%,69.57%,95.45%, While the positiveexpression rates of Bax protein were93.75%,47.83%,13.64%.Two two phase between thethree groups have significant difference (P <0.05).Cervical cancer patients, and also it isdivided into accompanied by lymph node metastasis group and without lymph nodemetastasis group.Fhit protein negative expression rates were92.86%,65.96%.Between thetwo groups have significant difference (P <0.05).The positive expression rates of Bcl-2protein are92.86%,57.45%. Between the two groups have significant difference (P <0.05).The positive expression rates of Bax protein were21.43%,53.32%.Between the twogroups had significant difference (P <0.05).(3) In61cases of cervical carcinoma,15cases ofcervical adenocarcinoma, Fhit protein negative expression rate is60%,46cases of cervicalsquamous cell carcinoma tissue, Fhit protein positive expression rate was76.09%.Thepositive expression rates of Bcl-2protein are53.33%,69.57%.The positive expression ratesof Bax protein were60%and43.48%.Two pathological types were no significantdifferences (P>0.05).(4) The experimental results shou in cervical carcinoma tissueswith Fhit protein negative expression and Bcl-2protein positive expression were positivelycorrelated (rs=0.319, P <0.05),while the positive rate of Bax protein expression wasnegatively correlated.And there was a significant difference (rs=-0.287, P <0.05).Conclusion:1, The negative expression of Fhit protein may be involved in the occurrence anddevelopment of cervical cancer.2, The negative expression of Fhit protein relate with cervical cancer clinical staging,histological differentiation and lymph node metastasis. Through the detection of cervicalcancer tissue in the expression of Fhit protein, to judge the malignant degree and prognosisof cervical cancer has important significance.3, The negative expression of Fhit protein in cervical carcinoma tissues is unrelated tothe pathological type.4, Fhit protein no expression may be through the up-regulation of Bcl-2expressionand the down-regulation of Bax expression.increasing Bcl-2/Bax ratio,leading to excessiveapoptosis inhibition,leading to the cervical cancer.