组织芯片技术检测CMTM2在人睾丸肿瘤组织中的表达

目的 探讨CMTM2在人睾丸肿瘤组织中的蛋白表达及其临床病理学意义.方法 运用组织芯片技术、免疫组织化学方法检测CMTM2在人睾丸肿瘤组织和正常组织中的表达.结果 15例正常人睾丸对照组中11例(73.3%)CMTM2蛋白表达为阳性;26例精原细胞瘤中17例(65.4%)CMTM2蛋白表达为阳性;7例畸胎瘤中4例(57.1%)CMTM2蛋白表达为阳性;12例胚胎癌中3例(25.0%)CMTM2蛋白表达为阳性;10例卵黄囊瘤中4例(40.0%)CMTM2蛋白表达为阳性.胚胎癌、卵黄囊瘤组与正常人睾丸对照组相比较,两组间具有显著性意义(P<0.05).而精原细胞瘤实验组以及畸胎瘤实验组与正常人睾丸对照组相比较,没有显著性差异(P>0.05).结论 CMTM2蛋白在胚胎癌,卵黄囊瘤中的表达水平较正常对照睾丸组织显著降低,CMTM2可能为睾丸肿瘤候选的抑癌基因.     

睾丸肿瘤156例临床统计

1957～1988年大阪大学泌尿科收治生殖细胞性睾丸肿瘤154名,其中单侧性151名(右76,左74,不明1),双侧性3名,1名双侧病理性质相同,考虑一侧由另一侧转移所致,另2例双侧病理性质不同。故154名患者按156例肿瘤统计。病理组织学分为单一组织型和复合组织型。前者114例(73.1%),包括胚胎性癌16例(10.3%)、畸胎瘤13例(8.3%)、卵黄囊肿瘤5例(3.2%)。后者42例(26.9%),包括与胚胎性癌、畸胎瘤、绒毛癌混合等。为方便计,按Dixon及Moore分类法,分为精原细胞瘤和非精原细胞瘤。年龄分布;非精原细胞瘤呈双峰型,5岁以前、     

Is期睾丸混合性生殖细胞瘤不同治疗方法研究(附3例报告)

目的:本文旨在探讨Is期睾丸混合性生殖细胞瘤的不同治疗方法。方法:对2008年2月至2012年6月收治3例(年龄26~39岁)入院的Is期睾丸混合性生殖细胞瘤患者的临床资料进行回顾性分析和总结,并结合文献就该期肿瘤的临床特征进行探讨。结果:3例患者中1例只行根治性睾丸切除术,1例行根治性睾丸切除术+腹膜后淋巴结清扫术+BEP方案化疗,1例行根治性睾丸切除术+放疗。混合性生殖细胞瘤病理成分分别为左侧95%未成熟畸胎瘤、精原细胞瘤合并5%绒癌、胚胎性癌成分,左侧75%精原细胞瘤合并25%胚胎性癌、畸胎瘤成分,右侧90%成熟性畸胎瘤合并10%卵黄囊瘤。随访24个月3例患者肿瘤无局部复发和远处转移。结论:对于Is期睾丸混合性生殖细胞瘤诊断主要依靠体格检查、超声、MRI、血清肿瘤标记物测定等,确诊需要病理学检查,根治性睾丸切除术是其基础的治疗方法。     

免疫组化染色及FISH检测12号染色体短臂捕获对Ⅱ型睾丸生殖细胞肿瘤的诊断意义

目的:分析Ⅱ型睾丸生殖细胞肿瘤(TGCT)的各亚型病理形态以及免疫组化特点、分子生物学改变,探讨免疫组化染色(IHC)及荧光原位杂交(FISH)检测在TGCT诊断分型中的意义。方法:收集97例TGCT(含有精原细胞瘤成分75例,胚胎癌成分17例,卵黄囊瘤成分11例,成熟性畸胎瘤16例,未成熟畸胎瘤3例,表皮囊肿1例),正常睾丸组织20例,以及非生殖细胞肿瘤的睾丸肿瘤6例。通过IHC检测TGCT各亚型对于不同抗体的阳性表达情况,并运用FISH技术检测各亚型中12号染色体短臂等臂和扩增的发生率。结果:TGCT各亚型的免疫表型各有不同,人类婆罗双树样基因-4(SALL4)及胎盘碱性磷酸酶(PLAP)最广谱、敏感性高,CD117及人八聚体结合转录因子4(OCT4)在浸润性精原细胞瘤和原位生殖细胞瘤(GCNIS)中强阳性表达,而在正常生精小管不表达。卵黄囊瘤显著表达人磷脂酰肌醇蛋白聚糖3(GPC3),表达范围和强度均优于人调节T细胞特异转录因子3(GATA3)和甲胎蛋白(AFP)。胚胎癌表达人广谱细胞角蛋白(CKpan)、OCT4、CD30。绒癌表达人绒毛膜促性腺激素(h CG)。浸润性TGCT中12号染色体短臂发生等臂和扩增的阳性率为96.7%(29/30)。结论:临床病理工作中,绝大部分病例单凭组织形态观察即可诊断TGCT,IHC检测利于更精确的分型,对于个体化治疗选择和预后评估意义重大。12号染色体短臂捕获是Ⅱ型TGCT的特异性分子改变,有助于排除其他病变。     

人类睾丸精原细胞瘤组织中P53基因突变和Rb基因蛋白产物表达…

采用Ｗｅｓｔｅｒｎ印迹和ＤＮＡ聚合酶链反应－单股构造多态性分析法和１７例人睾丸精原细胞瘤组织标本的抗癌基因Ｒｂ表达的蛋白产物和Ｐ５３基因外显子５～８的突变进行检测，发现有３例标本的Ｒｂ基因表达的蛋白产物缺失，有４例标本的Ｐ５３基因有点突变，对照的正常人睾丸组织和视网膜组织均呈Ｒｂ基因蛋白产物表达阳性，对照的正常人睾丸组织中未发现Ｐ５３基因突变。本结果提示人睾丸精原细胞瘤的发生与抗癌基因Ｒｂ蛋白产物     

小儿睾丸肿瘤临床分析(附55例报告)

目的　总结小儿睾丸肿瘤的诊治经验。　方法　回顾分析 5 5例睾丸肿瘤的临床资料。患儿年龄 2个月～ 12岁。多以无痛性阴囊肿块就诊。其中卵黄囊瘤 2 5例 ,畸胎瘤 2 4例 ,淋巴瘤 2例 ,精原细胞瘤 1例 ,皮样囊肿 2例 ,淋巴管瘤 1例。　结果　 5 5例中获随访 31例 ,平均随访 3年。包括卵黄囊瘤 17例 ,其中Ⅰ期 9例 ,仅做高位精索切断睾丸切除术 ;Ⅳ期 1例及复发瘤 7例中的 3例经化疗及手术健康存活。畸胎瘤 14例 ,其中行保留睾丸的畸胎瘤摘除术 5例 ,恶性畸胎瘤 1例 ,均无瘤存活。　结论　卵黄囊瘤Ⅰ期宜行单纯睾丸切除术 ,Ⅱ～Ⅳ期应联合应用PVB(顺铂加长春新碱加博来霉素或足叶乙甙 )化疗方案。小部分畸胎瘤病例可行肿瘤摘除术而保留睾丸组织。     

人类睾丸精原细胞瘤组织中P_（53）基因突变和Rb基因蛋白产物表达的缺失

采用Ｗｅｓｔｅｒｎ印迹和ＤＮＡ聚合酶链反应－单股构造多态性分析法对１７例人睾丸精原细胞瘤组织标本的抗癌基因Ｒｂ表达的蛋白产物和Ｐ_（５３）基因外显子５～８的突变进行检测，发现有３例标本的Ｒｂ基因表达的蛋白产物缺失，有４例标本的Ｐ_（５３）基因有点突变，对照的正常人睾丸组织和视网膜组织均呈Ｒｂ基因蛋白产物表达阳性，对照的正常人睾丸组织中未发现Ｐ_（５３）基因突变。本结果提示人睾丸精原细胞瘤的发生与抗癌基因Ｒｂ蛋白产物表达的缺失和Ｐ_（５３）基因的突变有关。     

Fas在正常睾丸组织及精原细胞瘤中的表达

目的 :明确Fas在正常睾丸组织及精原细胞瘤中的表达情况。　方法 :采用免疫细胞化学、原位杂交、反转录PCR(RT PCR)法检测 8例正常睾丸组织及 34例精原细胞瘤组织中Fas蛋白及FasmRNA的表达。　结果 :免疫组织化学方法发现在正常睾丸组织中的 3类主要细胞 (Leydig细胞、Sertoli细胞及生殖细胞 )中均有Fas分子表达 ;免疫组织化学和原位杂交方法在精原细胞瘤中检测到Fas表达阳性率分别为 41.18%和 38.2 4% ,表达水平明显减低或丧失 ,多呈现小片状或点状表达 ;RT PCR方法证明正常人睾丸组织中有FasmRNA的表达。　结论 :Fas在精原细胞瘤中的表达明显减少或丧失可能是精原细胞瘤形成及进展的原因。     

睾丸卵黄囊瘤的超声诊断

睾丸肿瘤分原发性和继发性两类，后较为罕见。原发性睾丸肿瘤属生殖细胞肿瘤，主要见于青壮年，多为精原细胞瘤，非精原细胞瘤临床较少见，主要包括睾丸绒毛膜上皮癌、畸胎瘤、睾丸卵黄囊瘤等。     

睾丸肿瘤的诊断

目的 :提高睾丸肿瘤的诊断水平。　方法 :回顾 1 992年 9月～ 2 0 0 1年 1 2月睾丸肿瘤 57例病人的症状、体征 ,影像学、肿瘤标记物和病理资料。　结果 :1 8例病人 (31 .3 % )延迟就医。术前查甲胎蛋白 (AFP) 1 1例 ,5例阳性。检测绒毛膜促性腺激素亚单位 (β HCG) 6例 ,1例阳性。二维B超及彩色多普勒血流显像超声 (CDFI)的灵敏度分别为 93 .5 % (45/ 4 7)、96 .4 % (2 8/ 2 7)。 55例行根治性睾丸切除术 ,2例行单纯睾丸切除术。后腹膜淋巴结清扫术 1 9例 ,淋巴结阳性 1 1例 ,阴性 8例。石蜡切片 57例 ,精原细胞瘤 2 2例 ,胚胎癌 9例 ,畸胎瘤 7例 ,卵黄囊瘤3例 ,混合性生殖细胞瘤 9例 ,恶性淋巴瘤 4例 ,其他 3例。其中 2 6例行术中冰冻切片 ,2 3例 (88.5 % )与石蜡切片报告符合。　结论 :病人需强化健康意识 ,尽早就医 ;术中常规冰冻切片 ,明确良、恶性肿瘤 ,是提高诊断水平 ,避免延误诊治的根本途径     

Pituitary‐tumour‐transforming‐gene 1 expression in testicular cancer

Genomic instability is a feature of germ cell tumours. The pituitary‐tumour‐transforming‐gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin‐fixed and paraffin‐embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti‐PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1‐positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesis.     

Histology in mixed germ cell tumors. Is there a favorite pairing?

PURPOSE: Mixed germ cell tumors account for approximately 30% to 50% of testicular tumors. To our knowledge a systematic review with statistical analysis of the associations of histological subtypes in mixed germ cell tumors has not been done previously. It was our impression that such associations exist. Delineating concordant histological types may provide insight into the ontogeny of testicular tumors and also have important clinical implications. MATERIALS AND METHODS: We retrospectively reviewed the testis cancer data base at our institution. The primary tumor of orchiectomy specimens was examined in 2589 patients. Of these patients mixed histology was noted in 1765 (68.2%). ORs were calculated for all possible combinations of teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and seminoma. In addition, we evaluated the association of various histological types with teratoma at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: Of 10 possible combinations of histological types in the primary tumor, positive correlations were noted in 4. The strongest correlation was found between teratoma and yolk sac tumor (OR 2.58, p <0.001). Teratoma or yolk sac tumor in the testis was associated with teratoma in the pathology specimen at post-chemotherapy retroperitoneal lymph node dissection. CONCLUSIONS: The strongest associations of histological subtypes in mixed germ cell tumors were seen between yolk sac tumor and teratoma. Similar associations are seen in late relapse and in some cases of prepubertal tumors. Further study of these associations may prove valuable in understanding the biology and clinical behavior of germ cell tumors.     

Significance of DNA quantification in testicular germ cell tumors

A cytophotometric quantification of DNA in tumor cells was performed in histological sections of orchidectomy specimens from 36 men with testicular germ cell tumors (TGCT), 7 of them showing more than one tumor type. Among the variants of seminoma (classic and spermatocytic) the lowest DNA content were in spermatocytic seminoma. With respect to non-seminomatous tumors (yolk sac tumor, embryonal carcinoma, teratoma, and choriocarcinoma), choriocarcinomas showed the highest DNA content, and the lowest value was found in teratomas. No significant differences were found between the average DNA content of seminomas (all types) and non-seminomatous tumors (all types). Both embryonal carcinoma and yolk sac tumor showed similar DNA content when they were the sole tumor and when they were found associated with other tumors. In this study, except for the 4 cases of teratoma and the case of spermatocytic seminoma, all TGCT examined did not show modal values of DNA content in the diploid range. Such an elevated frequency of aneuploidism in these tumors may be helpful for their diagnosis.     

Serum lactate dehydrogenase and its isoenzymes in men with maldescended testes

Serum lactate dehydrogenase and lactate dehydrogenase isoenzymes were determined as a screen for testicular germ cell neoplasia in 130 men with maldescended testes. A testicular tumor was found on clinical examination in 1 patient, which was revealed to be embryonal carcinoma, teratoma, yolk sac tumor and carcinoma in situ on orchiectomy. Subclinical testicular germ cell neoplasia was found on testicular biopsy in 3 men (1 with microinvasive seminoma and 2 with carcinoma in situ). These 4 patients had normal serum lactate dehydrogenase and serum lactate dehydrogenase isoenzymes. Elevated serum lactate dehydrogenase was noted in 3 men without testicular germ cell neoplasia: 1 had predominantly increased serum lactate dehydrogenase isoenzymes 1 to 3 and 2 had slightly increased serum lactate dehydrogenase isoenzymes 3 and 4. Serum lactate dehydrogenase and lactate dehydrogenase isoenzymes were not sensitive to detect testicular germ cell tumors in a subclinical stage.     

Subtype-specific incidence of testicular cancer in Germany: a pooled analysis of nine population-based cancer registries

Comparisons of incidence estimates of testicular cancer subtypes beyond seminoma and non-seminoma are virtually missing in the epidemiologic literature. We analysed incidence data from population-based German cancer registries to provide subtype-specific incidences of testicular cancer. We pooled data from nine cancer registries from 1998 to 2003. We estimated incidence and mortality time trends of West and East Germany. Incidence and mortality were standardized by the European standard population. The annual percentage incidence change from 1961 through 1989 was 4.9% in East Germany and 3.0% from 1970 through 2004 in Saarland. Incidence increases were the most pronounced among adolescents and young men aged 15–49 years. In 1998–2003, the seminoma incidence rate was 5.1 per 100 000; among non-seminomas, the rates were the highest for malignant teratoma (1.6 per 100 000), followed by embryonal carcinoma (1.2 per 100 000). Testicular lymphomas were rare (0.1 per 100 000). The incidence of testicular cancer among children aged 0–14 years was nearly constant from 1987 through 2004. Majority of these cancers were yolk sac tumours (0.1 per 100 000). In East and West Germany, rates of embryonal carcinoma in the early periods were considerably lower than the rates of malignant teratoma. In the most recent periods, rates of embryonal carcinoma became quite similar to the rates of malignant teratoma. The mortality decline started in West Germany roughly 12 years earlier than in East Germany. The later start of the mortality decline in East Germany may be because of a later introduction of platinum-based chemotherapy compared to West Germany.     

A case report: simultaneous bilateral testicular tumors with different cell types--complete response after combination chemotherapy of cisplatin and irrinotecan hydrochloride--

A 38-year-old man was admitted to our hospital complaining of bilateral scrotal swelling. On examination, the patient was found to have bilateral testicular tumors with jugular chain lymph node and para-aortic lymph node metastasis. He underwent bilateral inguinal orchiectomy. Histopathological examination of the excised tumors revealed seminoma, embryonal carcinoma, yolk sac tumor and immature teratoma in the right testis and seminoma in the left testis. The patient was treated postoperatively with two courses of BEP (bleomycin, etoposide, cisplatin) therapy and two courses of EP (etoposide, cisplatinum) therapy. The patient had lung metastasis during the follow-up period and we treated him with salvage combination chemotherapy of cisplatin and irinotecan hydrochloride (CPT-11). After the third course of cisplatin and CPT-11 chemotherapy the lung metastasis disappeared and we performed retroperitoneal lymph node dissection. The patient has remained free of disease 11 months after discharge.     

Testicular teratoma with nephroblastoma component

We report the development of Wilms' tumor in an atrophic testis and review the potential molecular pathogenesis. An 18-year-old man presented with 2 days of right testicular pain and growth in his atrophic testis. Ultrasonography revealed a heterogeneous mass. The chest radiographic findings and testicular tumor marker levels were normal. He underwent radical orchiectomy, with the pathologic examination showing teratoma with a nephroblastoma component, focal embryonal carcinoma, and minute yolk sac tumor. The development of Wilms' tumor in the testis is rare and can be explained by the activation of the WT1 gene during embryogenesis.     

Results of retroperitoneal lymph node dissection after chemotherapy in patients with pure seminoma in the orchidectomy specimen but elevated serum α‐fetoprotein

OBJECTIVE

To determine the incidence of necrosis, teratoma, and active cancer in specimens at retroperitoneal lymph node dissection (RPLND) after chemotherapy in patients who presented with a pure seminoma primary tumour and an elevated serum α‐fetoprotein (AFP) level at diagnosis who underwent surgery.

PATIENTS AND METHODS

A retrospective review of the Indiana University testis cancer database from 1980 to 2004 was performed to identify all patients with metastasic germ cell cancer, pure seminoma in the orchidectomy specimen, and an elevated AFP level. In all, 42 patients were identified; two with nonseminomatous germ cell cancer in the contralateral testicle were excluded.

RESULTS

RPLND pathology in the 40 patients showed necrosis in 13 (32.5%), teratoma in 12 (30%), and cancer in 15 (37.5%). The histological subtype of the 15 cancer specimens at RPLND was pure seminoma in two, embryonal in three, yolk sac in seven, variant in one, and mixed elements in two (one with seminoma and yolk sac, and one with embryonal and variant). In all, 20 patients presented with a serum AFP level of <1000 µg/mL with nine (45%) having teratoma only in the retroperitoneum in contrast to 20 patients with an AFP level of >1000 µg/mL with three (15%) having teratoma only in the retroperitoneum (P = 0.04). The level of serum AFP did not predict for active cancer in the retroperitoneum (P = 0.5).

CONCLUSIONS

RPLND in patients after chemotherapy who presented with pure seminoma in the orchidectomy specimen and an elevated AFP do not have a high probability of finding necrosis only in the RPLND specimen. In fact, the prevalence of persistent cancer is higher compared with the general group of patients that have RPLND after chemotherapy.