Expression And Clinical Significance Of TMPRSS2-Ets Fusion Gene In Prostate Cancer

Objectives： This study was designed to detect the expression of fusion geneTMPRSS2/ERG, TMPRSS2/ETV1and TMPRSS2/ETV4and protein TMPRSS2ERG and ETV1protein in prostate cancer and non-cancer prostate tissues [prostaticintraepithelial neoplasm(PIN), benign prostatic hyperplasia(BPH) and normalprostate], to investigate their relationship with prostate cancer and the role in theoccurrence and development of prostate cancer, to provide theoretical basis tofurther define the prostate cancer pathogenesis and to investigate new diagnosis andprevention and cure．Methods:14cases of archived BPH operation excision inparaffin-embedded,4cases of autopsy prostate specimens,70cases of prostate cancerwithout preoperative radiotherapy and chemotherapy,10cases of PIN inparaffin-embedded specimens were selected Randomly from University of SouthChina Department of pathology and The first people’s hospital pathologydepartment of Xiangtan from2005to2010. The expression of TMPRSS2/ERG,TMPRSS2/ETV1and TMPRSS2/ETV4fusion gene was detected by tissue chiptechnology and fluorescence in situ hybridization; The expression of TMPRSS2, ERGand ETV1proteins was detected by immunohistochemistry; and integrated clinicpathological characteristics were analyzed. Statistical Methods: SPSS16.0package forstatistical analysis. χ2test and Fisher ’ s exact probability were used to analyze theexperimental data of immunohistochemistry and in situ hybridization, Spearman’scorrelation analysis were used to analyze the correlation among the indexes. Thedifference was statistically significant if P <0.05.Results:1.Immunohistochemistry showed：1.1TMPRSS2, ERG and ETV1were positive expressed in benign prostate, PIN and prostate cancer. TMPRSS2positive staining was localized in cell membraneand/or cytoplasm. The positive expression rate of TMPRSS2had no significantdifferences among benign prostate (56.0%,10/18), among benign prostate, PIN(100.0%,10/10) and prostate cancer (83.3%,58/70). ERG positive staining waslocalized in the nucleus, the positive expression rates of ERG were significantdifferences among benign prostate(0%，0/10), PIN (30.0%，3/10)and prostatecancer(81.4%，57/70)(P<0.01). ETV1positive staining was localized in the nucleus,The positive expression rate of ETV1were significant differences among benignprostate(22.2%,4/18), PIN (50.0%,5/10) and prostate cancer(68.6%,48/70)(P＜0.05),the expression rate of prostate cancer group was higher than benign prostate group.1.2The relation of TMPRSS2, ERG and ETV1protein expression and clinicpathological features.There was no significance differences between TMPRSS2expression and age(P＞0.05), the expression rate of TMPRSS2also increased with increasing Gleasonscore with statistically significant (P＜0.01, r=0.493); and TMPRSS2expression wererelated to clinical staging with statistically significant (P＜0.05, r=0.248). There wasno significance differences between ERG expression and age(P＞0.05), theexpression rate of ERG also increased with increasing Gleason score and clinicalstaging progress, was related to Gleason score(P＜0.05, r=0.445) and clinicalstaging(P＜0.01, r=0.360) with statistically significant; and TMPRSS2expressionwere related to clinical staging with statistically significant (P＜0.05, r=0.248). Therewas no significance differences between ERG expression and age(P＞0.05).Therewas significance differences between ETV1expression and age(P＞0.05), ETV1expression was related to Gleason score(P＜0.01, r=0.456) with statisticallysignificant; accompanied by clinical staging, the expression rate was increasing andwas positively correlated, differences was statistically significant(P<0.01).1.3The correlation of TMPRSS2, ERG and ETV1in prostate cancer.Spearman’s correlation analysis was used to analyze the correlation amongindexes, the results showed；TMPRSS2is positive correlated with ERG in prostate cancer(r=0.465,P＜0.01); TMPRSS2is positive correlated with ETV1in prostatecancer(r=0.465,P＜0.01); ERG is not correlated with ETV1in prostate cancer.2. The result of FISH showed:2.1TMPRSS2/ERG fusion gene was positive expressed in prostate cancer group,negative expressed in benign prostate, the positive expression rate of TMPRSS2/ERGfusion gene in prostate cancer group, PIN group and benign prostate group was54.3%，10.0%，0.0%respectively, differences was statistically significant(P<0.01);TMPRSS2-ETV1was positive expressed in prostate cancer group, negative expressedin PIN group and benign prostate, the positive expression rate was24.3%，0.0%，0.0%respectively, differences was statistically significant(P<0.05); TMPRSS2-ETV4was positive expressed in prostate cancer group, negative expressed in PIN group andbenign prostate, the positive expression rate was24.3%，0.0%，0.0%respectively,differences was not statistically significant(P<0.05)2.2The collection of TMPRSS2-ERG, TMPRSS2-ETV1and TMPRSS2-ETV4protein expression and clinic pathological features.There was no statistical significance between positive rate of the expression ofTMPRSS2-ERG fusion gene and age(P＞0.05). There was statistical significancesbetween positive rate of the expression of TMPRSS2-ERG fusion gene and Gleasonscore and clinical staging (P<0.05). There was no statistical significance betweenpositive rate expression of TMPRSS2-ETVI fusion gene and age; the positive rateexpression of TMPRSS2-ETVI fusion gene was related to Gleason score withstatistical significances; accompanied by clinical staging, the expression rate wasincreasing, statistical significances(P＜0.05); There was no statistical significanceamong positive rate expression of TMPRSS2-ETVI fusion gene, age, Gleason scoregroup and clinic staging(P＞0.05).2.3The collection of TMPRSS2-ERG, TMPRSS2-ETV1and TMPRSS2-ETV4fusion genes in prostate cancer.In this study, the correlation analysis among those three fusion genes,TMPRSS2-ERG fusion gene was positive correlation with TMPRSS2-ETV1fusion gene in prostate cancer with statistical significances (r=0.319,P＜0.01);TMPRSS2-ERG was not correlation with TMPRSS2-ETV4in prostate cancer with nostatistical significances(r=-0.015,P＞0.05). TMPRSS2-ETV1was not correlation withTMPRSS2-ETV4in prostate cancer with no statistical significances(r=0.103, P＞0.05).Conclusions:1.1.Protein TMPRSS2, ERG and ETV1and fusion genes TMPRSS2-ETS wereup regulated in prostate cancer.2. TMPRSS2, ERG, ETV1proteins and TMPRSS2-ERG, TMPRSS2-ETV1fusion genes may participated in tumorigenesis,differentiation and development.