性发育异常发生性腺肿瘤的分子靶标筛选
发布时间：2019-03-17 15:04
【摘要】：研究背景性发育异常疾病是一种先天性疾病,可以表现为染色体核型、性腺、解剖上的性别异常,发病率在1/4500～1/5000,具有独特的临床特点和生物学行为,以患者年轻,预后好,生存期长为特点。多数发表的研究来自欧美国家,在中国开展的研究和数据较少。研究目的1)建立我院DSD患者数据库,进行临床数据分析。2)对比DSD患者发生肿瘤与未发生肿瘤的性腺组织标本,采取免疫组化的方法,进行相关分子标志物研究和分析。研究方法1、检索我院自1984年10月至2014年10月手术切除性腺的DSD患者,通过病例回顾收集临床病理资料,分析DSD患者的临床病理特点和预后。2、选取于我院留存的发生肿瘤的DSD患者性腺蜡块标本及未发生肿瘤DSD患者标本,进行免疫组化染色,分析PLAP、α-inhibin、OCT4、SOX9、FOXL2五种分子标记物的表达情况,并分析其与临床病理特点的相关性及对预后的影响。研究结果1、291例手术患者平均年龄为19.1±6.3岁,身高中位数为165cm, BMI中位数为19.98kg/m2,三种因素在肿瘤组和非肿瘤组统计学P值均0.05。2、腺瘤患者均发生于46,XY染色体DSD患者,其临床表现及免疫组化上均与无瘤患者相似。3、DSD患者性腺肿瘤发生率为12.0%,好发于左侧(51.4%)及盆腔内(88.6%,P0.001)。4、手术结合顺铂+长春新碱+博来霉素(PVB)和(或)博来霉素+足叶乙苷+顺铂(PEB)联合化疗方案可使肿瘤患者治愈率达100%。5、28例肿瘤患者平均随访73.5±73.0个月。6、DSD肿瘤患者存在较重社会心理压力造成术后生活质量受损。7. α-inhibin、SOX9、FOXL2、OCT4、PLA P在肿瘤性腺和非肿瘤性腺中表达P值分别为0.248、0.338、0.049、0.001、0.001；同时α-inhbibin在XY核型下肿瘤性腺中表达减低(P=0.019)；FOXL2在XY核型下肿瘤组和非肿瘤间表达P值为0.056。结论DSD患者性腺发生肿瘤的百分比为12.0%,与发病年龄、BMI不相关。部位上好发于左侧,盆腔内发多见,预后好但存在术后生活质量受损,主要表现为社会心理方面。OCT4、PLAP具有较好的肿瘤标志意义,α-inhibin在XY肿瘤性腺中表达明显减低,SOX9肿瘤标志意义不大,FOXL2尚需进一步研究。
[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, 伪-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 卤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 卤73.0 months, with a mean follow-up of 73.5 卤73.0 months. Severe psychosocial stress in patients with DSD tumor resulted in impaired quality of life after operation. 7. 5%. The expression of 伪-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 伪-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 伪-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 伪-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.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R730.26;R588
本文编号：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, 伪-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 卤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 卤73.0 months, with a mean follow-up of 73.5 卤73.0 months. Severe psychosocial stress in patients with DSD tumor resulted in impaired quality of life after operation. 7. 5%. The expression of 伪-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 伪-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 伪-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 伪-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.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R730.26;R588
【参考文献】
相关期刊论文 前1条
1 葛秦生，，谷春霞，叶丽珍，林守清，何方方，郁琦;推荐一种性发育异常的分类[J];生殖医学杂志;1994年03期
本文编号：2442414
本文链接：https://www.wllwen.com/yixuelunwen/zlx/2442414.html
