性發(fā)育異常發(fā)生性腺腫瘤的分子靶標篩選
發(fā)布時間：2019-03-17 15:04
【摘要】：研究背景性發(fā)育異常疾病是一種先天性疾病,可以表現(xiàn)為染色體核型、性腺、解剖上的性別異常,發(fā)病率在1/4500～1/5000,具有獨特的臨床特點和生物學行為,以患者年輕,預后好,生存期長為特點。多數(shù)發(fā)表的研究來自歐美國家,在中國開展的研究和數(shù)據(jù)較少。研究目的1)建立我院DSD患者數(shù)據(jù)庫,進行臨床數(shù)據(jù)分析。2)對比DSD患者發(fā)生腫瘤與未發(fā)生腫瘤的性腺組織標本,采取免疫組化的方法,進行相關分子標志物研究和分析。研究方法1、檢索我院自1984年10月至2014年10月手術(shù)切除性腺的DSD患者,通過病例回顧收集臨床病理資料,分析DSD患者的臨床病理特點和預后。2、選取于我院留存的發(fā)生腫瘤的DSD患者性腺蠟塊標本及未發(fā)生腫瘤DSD患者標本,進行免疫組化染色,分析PLAP、α-inhibin、OCT4、SOX9、FOXL2五種分子標記物的表達情況,并分析其與臨床病理特點的相關性及對預后的影響。研究結(jié)果1、291例手術(shù)患者平均年齡為19.1±6.3歲,身高中位數(shù)為165cm, BMI中位數(shù)為19.98kg/m2,三種因素在腫瘤組和非腫瘤組統(tǒng)計學P值均0.05。2、腺瘤患者均發(fā)生于46,XY染色體DSD患者,其臨床表現(xiàn)及免疫組化上均與無瘤患者相似。3、DSD患者性腺腫瘤發(fā)生率為12.0%,好發(fā)于左側(cè)(51.4%)及盆腔內(nèi)(88.6%,P0.001)。4、手術(shù)結(jié)合順鉑+長春新堿+博來霉素(PVB)和(或)博來霉素+足葉乙苷+順鉑(PEB)聯(lián)合化療方案可使腫瘤患者治愈率達100%。5、28例腫瘤患者平均隨訪73.5±73.0個月。6、DSD腫瘤患者存在較重社會心理壓力造成術(shù)后生活質(zhì)量受損。7. α-inhibin、SOX9、FOXL2、OCT4、PLA P在腫瘤性腺和非腫瘤性腺中表達P值分別為0.248、0.338、0.049、0.001、0.001；同時α-inhbibin在XY核型下腫瘤性腺中表達減低(P=0.019)；FOXL2在XY核型下腫瘤組和非腫瘤間表達P值為0.056。結(jié)論DSD患者性腺發(fā)生腫瘤的百分比為12.0%,與發(fā)病年齡、BMI不相關。部位上好發(fā)于左側(cè),盆腔內(nèi)發(fā)多見,預后好但存在術(shù)后生活質(zhì)量受損,主要表現(xiàn)為社會心理方面。OCT4、PLAP具有較好的腫瘤標志意義,α-inhibin在XY腫瘤性腺中表達明顯減低,SOX9腫瘤標志意義不大,FOXL2尚需進一步研究。
[Abstract]:The study of background sexual dysplasia is a congenital disease, which can be manifested as chromosome karyotype, gonad, anatomical sex abnormality. The incidence rate is 1? 500? 000? 1? 000. It has unique clinical characteristics and biological behavior, and the patient is young, and the patient is young. The prognosis is good and the survival time is long. Most published research comes from European and American countries, and few research and data are carried out in China. Objective 1) to establish the database of DSD patients in our hospital and analyze the clinical data. 2) to compare the gonadal tissue specimens of DSD patients with and without tumors, and to study and analyze the related molecular markers by immunohistochemical method. Methods 1. We searched the patients with DSD who underwent gonadectomy from October 1984 to October 2014 in our hospital. The clinicopathological data were collected retrospectively to analyze the clinicopathological features and prognosis of patients with DSD. The expression of five molecular markers of PLAP, 偽-inhibin,OCT4,SOX9,FOXL2 was analyzed by immunohistochemical staining in the samples of gonadal wax from DSD patients and non-tumor patients with DSD, which were retained in our hospital. The correlation with clinicopathological features and prognosis were also analyzed. Results the average age was 19.1 鹵6.3years, the median height was 165cm, and the median BMI was 19.98kg / m2. The three factors were statistically significant (P < 0.05.2) in the tumor group and the non-tumor group. The clinical and immunohistochemical features of XY chromosome DSD patients were similar to those of non-tumor patients. 3. The incidence of gonadal tumors was 12.0% in the patients with DSD.The incidence rate of gonadal tumors was 51.4% in the left side and 88.6% in the pelvis (P0.001). Combined with cisplatin-vincristine (PVB) and / or bleomycin-etoposide-cisplatin-(PEB) combined with chemotherapy, the cure rate of tumor patients was 100%. The mean follow-up period of 28 tumor patients was 73.5 鹵73.0 months, with a mean follow-up of 73.5 鹵73.0 months. Severe psychosocial stress in patients with DSD tumor resulted in impaired quality of life after operation. 7. 5%. The expression of 偽-inhibin,SOX9,FOXL2,OCT4,PLA P in tumor gonads and non-tumor gonads was 0.248, 0.338, 0.049, 0.001,0.001, respectively, and the expression of 偽-inhbibin in tumor gonads was decreased under XY karyotype (P < 0.019). The expression of FOXL2 between tumor group and non-tumor group under XY karyotype was 0.056. Conclusion the percentage of gonadal tumors in patients with DSD is 12.0%, which is not correlated with age of onset and BMI. OCT4 and PLAP have good tumor marker significance, and 偽-inhibin expression in the gonad of XY tumor is obviously decreased, but the prognosis is good, but the quality of life after operation is impaired, and the expression of 偽-OCT4 and OCT4 in the gonads of XY tumor is lower than that of OCT4, OCT4 and OCT4 is a good marker of tumor. SOX9 tumor markers are of little significance, and FOXL2 should be further studied.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R730.26;R588
本文編號：2442414
[Abstract]:The study of background sexual dysplasia is a congenital disease, which can be manifested as chromosome karyotype, gonad, anatomical sex abnormality. The incidence rate is 1? 500? 000? 1? 000. It has unique clinical characteristics and biological behavior, and the patient is young, and the patient is young. The prognosis is good and the survival time is long. Most published research comes from European and American countries, and few research and data are carried out in China. Objective 1) to establish the database of DSD patients in our hospital and analyze the clinical data. 2) to compare the gonadal tissue specimens of DSD patients with and without tumors, and to study and analyze the related molecular markers by immunohistochemical method. Methods 1. We searched the patients with DSD who underwent gonadectomy from October 1984 to October 2014 in our hospital. The clinicopathological data were collected retrospectively to analyze the clinicopathological features and prognosis of patients with DSD. The expression of five molecular markers of PLAP, 偽-inhibin,OCT4,SOX9,FOXL2 was analyzed by immunohistochemical staining in the samples of gonadal wax from DSD patients and non-tumor patients with DSD, which were retained in our hospital. The correlation with clinicopathological features and prognosis were also analyzed. Results the average age was 19.1 鹵6.3years, the median height was 165cm, and the median BMI was 19.98kg / m2. The three factors were statistically significant (P < 0.05.2) in the tumor group and the non-tumor group. The clinical and immunohistochemical features of XY chromosome DSD patients were similar to those of non-tumor patients. 3. The incidence of gonadal tumors was 12.0% in the patients with DSD.The incidence rate of gonadal tumors was 51.4% in the left side and 88.6% in the pelvis (P0.001). Combined with cisplatin-vincristine (PVB) and / or bleomycin-etoposide-cisplatin-(PEB) combined with chemotherapy, the cure rate of tumor patients was 100%. The mean follow-up period of 28 tumor patients was 73.5 鹵73.0 months, with a mean follow-up of 73.5 鹵73.0 months. Severe psychosocial stress in patients with DSD tumor resulted in impaired quality of life after operation. 7. 5%. The expression of 偽-inhibin,SOX9,FOXL2,OCT4,PLA P in tumor gonads and non-tumor gonads was 0.248, 0.338, 0.049, 0.001,0.001, respectively, and the expression of 偽-inhbibin in tumor gonads was decreased under XY karyotype (P < 0.019). The expression of FOXL2 between tumor group and non-tumor group under XY karyotype was 0.056. Conclusion the percentage of gonadal tumors in patients with DSD is 12.0%, which is not correlated with age of onset and BMI. OCT4 and PLAP have good tumor marker significance, and 偽-inhibin expression in the gonad of XY tumor is obviously decreased, but the prognosis is good, but the quality of life after operation is impaired, and the expression of 偽-OCT4 and OCT4 in the gonads of XY tumor is lower than that of OCT4, OCT4 and OCT4 is a good marker of tumor. SOX9 tumor markers are of little significance, and FOXL2 should be further studied.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R730.26;R588
【參考文獻】
相關期刊論文 前1條
1 葛秦生，，谷春霞，葉麗珍，林守清，何方方，郁琦;推薦一種性發(fā)育異常的分類[J];生殖醫(yī)學雜志;1994年03期
本文編號：2442414
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