前列腺癌E26转录因子家族基因融合发生率及其与临床病理指标相关性研究

Prevalence of ETS gene fusion in prostate cancer and its correlation with patients＇ clinicopathologic index

目的 探讨前列腺癌E26转录因子（E26 transformation-specific,ETS）家族基因融合的发生率及其与临床病理指标的相关性.方法 选取2010年10月至2012年2月确诊为前列腺癌患者的91例穿刺标本和18例根治性前列腺切除术标本.91例穿刺标本患者,年龄55～ 90岁,中位年龄75岁.中位PSA为33.4 μg/L,均值为118.8 μg/L;Gleason评分6～9分,中位数为7分;早、中期肿瘤（≤T2b期,无淋巴结及骨转移）32例（34％）,局部晚期肿瘤（＞T2b期,伴或不伴局部淋巴结转移,无骨转移）36例（40％）,远处转移肿瘤（M1期）23例（26％）.18例根治性前列腺切除术标本患者,年龄63～81岁,中位年龄72岁.PSA 5.0～46.2 μg/L,中位数为18.5 μg/L; Gleason评分6～9分,中位数为7分;TNM分期：T2期9例,T3期8例,T4a期1例.采用荧光原位杂交技术检测前列腺癌ETS基因TMPRSS2-ERG,TMPRSS2-ETV1和TMPRSS2-ETV4融合情况,比较基因融合阳性和阴性患者的年龄、TNM分期、Gleason评分、PSA值.结果 穿刺标本、根治标本的TMPRSS2-ERG融合发生率分别为14.3％ （13/91,95％CI 0.071～ 0.215）和11.1％ （2/18,95％ CI 0～ 0.256）,无TMP RSS2-ETV1和TMPRSS2-ETV4融合.TMPRSS2-ERG融合阳性病例中,缺失型融合模式为13例,插入型融合模式为7例,5例同时存在缺失型和插入型融合模式.5例缺失型融合模式患者出现了远处转移,其中1例同时存在插入型融合模式,无单纯插入型融合模式患者出现远处转移.融合阳性和阴性患者在年龄（P=1.000）、TNM分期（P=2.052）、主要Gleason评分（P=2.186）、Gleason评分（P=2.107）、PSA值（P=1.138）、前列腺癌危险度分级（P=2.597）方面差异均无统计学意义.结论 前列腺癌患者TMPRSS2-ERG融合阳性中缺失型融合比插入型融合更常见.TMPRSS2-ERG融合阳性和阴性患者在年龄、TNM分期、主要Gleason评分、Gleason评分、前列腺癌危险度分级等方面比较差异均无统计学意义.

Objective To explore the prevalence of ETS gene fusion in prostate cancer and its cor- relation with patient＇s elinieopathologie index. Methods Ninety-one samples from prostate needle biopsy cases with median age 75 （55-90） years and 18 samples from radical prostatectomy cases with median age 72 （63-81） years were collected from Oct. 2010 to Feb. 2012. TMPRSS2-ERG, TMPRSS2-ETV1 and TM- PRSS2-ETV4 fusions were tested by muhi-probe fluorescence in situ hybridization （FISH） assay. Fusion positive and negative cases were compared with age, TNM stage, Gleason score （median Gleason score 7 （6-9）） , and PSA value （median PSA 33.4 μg/L, mean PSA 118.8 μg/L）. In needle biopsy cases, there were early stage 32 （ 34% ） , locally advanced prostate cancer 36 （40%） , metastasis 23 （ 26% ） ; in radical prostatectomy cases, there were 9 cases in T2 stage, 8 cases in T3 stage, 1 cases in T4a stage, respectively. Results TMPRSS2-ERG fusions were present in 14.3% （ 13/91 , 95% confidence interval, 0.071-0.215）biopsy specimens and in 11.1% （2/18, 95% confidence interval, 0-0.256） radical prostatectomy speci- mens. No TMPRSS2-ETV1 or TMPRSS2-ETV4 fusions were found in any cases. Altogether, 13 （86.7%） eases possessed deletion pattern. And 7 （46.6%） hold insertion pattern. 5 eases had both deletion and inser- tion pattern. 38.5% （5/13） deletion pattern had distant metastasis. Except one metastatic ease harbored both deletion and insertion pattern, there was no insertion pattern accompanied with metastasis. There were no differences between fusion positive and negative eases in the distribution of age （P= 1.000） , PSA （P = 1.138） , primary Gleason score （ P= 2.186） , Gleason score （P= 2.107） , TNM stage （ P= 2.052） and Risk Degree （P= 2.597）. Conclusions The TMPRSS2-ERG fusion positive cases harbor more deletion pattern than insertion pattern. There are no differences between fusion positive and negative cases in the distribution of age, PSA, Gleason score, TNM stage and Risk Degree.