Screening for ovarian cancer

There has been considerable interest in the prospect of early detection of ovarian cancer through screening asymptomatic women, in both the general and 'high-risk' populations. Over the last decade screening strategies using the serum marker CA126 and transvaginal ultrasound have been refined and encouraging data have emerged on the impact of screening on ovarian cancer survival rates. Two randomized controlled trials are now underway in the general population to establish the impact of screening on ovarian cancer mortality while comprehensively tackling the issues of compliance, health economics and physical and psychological morbidity. In addition, trials in the high-risk population aimed at optimizing the current strategy have commenced in both the USA and the UK.     

Screening for ovarian cancer

The efficacy of ovarian cancer screening remains to be proven. Advances in ultrasound and tumor marker technology, combined with complex statistical analysis have facilitated 2 large ongoing randomized controlled trials of screening which are powered to determine the impact on mortality. Serum proteomics seems to be a promising area for biomarker discovery, but requires more rigorous validation before it can be used in clinical trials. Current screening tests, clinical trials in the general and high-risk populations, screening acceptability and costs are reviewed in this article.     

Screening for ovarian cancer

The increased survival advantage for patients diagnosed with early stage ovarian cancer suggests that screening programs that detect early stage disease might have an impact on disease mortality. Attempts are being made to develop effective screening methods for early ovarian cancer in women without symptoms, using a variety of serum tumour markers, proteomic patterns and ovarian vascular and morphological features. Three main screening strategies have emerged, one utilising transvaginal scanning as the primary test (ultrasound strategy), one involving measurement of the serum tumour marker CA125 as the primary test with transvaginal scanning as the secondary test (multimodal strategy) and another utilising both transvaginal scanning and measurement of CA125 together as both a primary and secondary test (combined strategy). Large randomised trials are now underway to provide definitive data on the impact of screening on mortality and address morbidity, health economics and psychosocial issues.     

Screening and detection of ovarian cancer

According to the National Cancer Institute, ovarian cancer is the sixth most common cancer in women and the leading cause of death from gynecologic malignancies. Most often the disease is advanced before symptoms are evident. It is estimated that only 15% to 30% of women in advanced stages will survive 5 years, whereas, of women in stage I at the time of diagnosis, 95% are likely to be alive in 5 years, and most are cured following surgery. Current screening techniques recommended for women with known strong risk factors include combination transvaginal sonography with cancer antigen (CA-125). Transvaginal sonography and serum CA-125 have limited diagnostic predictability. A new early detection method that uses proteomic technology will soon be available. The OvaCheck test, as researchers purport, is a highly specific and sensitive early detection method for ovarian cancer in women with strong risk factors. The Food and Drug Administration has yet to approve nationwide marketing of OvaCheck for early detection, because trials are not yet complete. Anticipated commercial availability is scheduled for early 2005.     

Screening for ovarian cancer in the general population

Screening for ovarian cancer in the general population presents several unique challenges. Without a clearly identified premalignant state, efforts have focused on detection of early stage disease. Towards this end, investigators have focused on the use of serum markers and transvaginal ultrasound. CA125 determination is the most reliable serum marker in use, and utilization of serial measurements to calculate risk of cancer appears to have greater utility than evaluation of a single value. Multimodality screening focuses on combining serial CA125 measurement with transvaginal ultrasound follow-up for those with abnormal values. Large prospective trials, such as the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), are currently underway to assess the impact of various screening strategies on mortality, and to evaluate feasibility, acceptability, and morbidity of screening. Future research efforts will undoubtedly focus on promising techniques to examine the serum proteosome for patterns to identify early ovarian cancer.     

Screening for ovarian cancer in the general population

Advances in screening and early detection of ovarian cancer over the past decade have included novel interpretation of serum CA125, discovery of human epididymis protein 4, which has the potential to add to CA125, and the growing understanding of the flaws of previous biomarker studies. No mortality effect was found in the ovarian screening arm of the Prostate Lung Colorectal and Ovarian Cancer Screening Trial.(87) Concerns, however, have been raised about trial design, and the results from the UK Collaborative Trial of Ovarian Cancer Screening in the general population(38) and other ongoing studies in the high-risk population are awaited for a definitive conclusion. Future work needs to take into account the new insights into ovarian cancer subtypes and the growing evidence that a significant proportion of ovarian cancers might originate in premalignant lesions in the distal fallopian tube.     

双向凝胶电泳-质谱技术行卵巢癌血浆标志物分析

目的 探索卵巢癌潜在的肿瘤标志物.方法 抽取2004年8月至2007年10月在北京大学第三医院就诊的卵巢浆液性乳头状囊腺癌20例血浆与对照组妇女20例血浆,去除血浆中的高丰度蛋白(白蛋白/IgG)后,采用离心超滤对两组血浆蛋白脱盐、浓缩;应用双向凝胶电泳-质谱技术(2-DE/MS)分离两组血浆样品,经图像分析软件对比两组间的差异蛋白后,通过液相色谱-质谱技术(LC-MS/MS)鉴定差异蛋白点,并与蛋白质数据库资料进行对比分析.结果 两组共发现11个差异蛋白点(两组间的蛋白表达强度升高或降低200%者定义为差异点),对其中4个分子质量较小的进行了鉴定,与蛋白质数据库对比后,发现为触珠蛋白、血红蛋白β亚基、载脂蛋白C-Ⅲ和甲状腺素运载蛋白.前两者在卵巢浆液性乳头状囊腺癌组血浆中表达上调,后两者表达下调.结论 触珠蛋白、血红蛋白β亚基、载脂蛋白C-Ⅲ、甲状腺素运载蛋白可能为卵巢癌潜在的肿瘤标志物,但尚需做深入研究.     

卵巢上皮性癌相关抗原的筛选和血清学检测

目的构建卵巢上皮性癌（卵巢癌）腹水肿瘤细胞的cDNA文库,从中筛选能用于卵巢癌早期诊断和免疫治疗靶点的卵巢癌相关抗原。方法用3例卵巢浆液性囊腺癌、1例卵巢黏液性囊腺癌、1例卵巢子宫内膜样癌患者的腹水肿瘤细胞构建cDNA文库,采用改良的重组克隆表达抗原的血清学鉴定（SEREX）技术与抑制性消减杂交（SSH）方法相结合的策略从文库中筛选卵巢癌相关抗原基因,并对其进行酶切鉴定、核苷酸测序分析。采用重组肿瘤抗原的微型血清学检测（SMARTA）法检测筛选出的卵巢癌相关抗原与96例卵巢癌患者和96例正常妇女的血清中相应自身抗体的阳性反应情况。结果经两轮血清学筛选和核苷酸测序分析,最终得到55个候选的卵巢癌相关抗原基因片段,代表45个基因,分为6类：（1）与已知的卵巢癌相关基因同源的基因,如BARD1基因等;（2）与其他肿瘤相关基因同源的基因,如TM4SF1基因等;（3）在一些特殊组织中表达的基因,如ILF3、FXR1基因等;（4）与一些特殊功能蛋白基因同源的基因,如TIZ、C1D基因等;（5）与胚胎来源的基因同源的基因,如PKHD1基因等;（6）其余为在基因库GenBank中无同源序列可比对的未知基因,如OV-189基因等。TM4SF1、C1D、BARD1、FXR1、OV-189基因的噬菌体重组融合抗原与卵巢癌患者血清中相应IgG型自身抗体反应的阳性率分别为28％、21％、23％、23％、31％,与正常妇女血清反应的阳性率分别为9％、6％、5％、8％、13％,分别比较,差异均有统计学意义（P〈0．01）;TIZ、FXR1、OV-189基因的重组抗原与卵巢癌患者血清中相应IgM型自身抗体反应的阳性率分别为26％、28％、18％,与正常妇女血清反应的阳性率分别为8％、11％、7％,分别比较,差异均有统计学意义（P〈0．05）。FXR1、OV-189基因的重组抗原与Ⅰ～Ⅱ期卵巢癌患者血清中相应IgG型自身抗体反应的阳性率（分别为34％、46％）高于Ⅲ～Ⅳ期者（分别为16％、23％）,两者分别比较,差异均有统计学意义（P值分别为0．045、0．021）;OV-189基因的重组抗原与高分化卵巢癌患者血清中相应IgG型自身抗体反应的阳性率（为67％）高于中～低分化者（为26％）,两者比较,差异均有统计学意义（P=0．001）。TIZ、FXR1基因的重组抗原与Ⅰ～Ⅱ期卵巢癌患者血清中相应IgM型自身抗体反应的阳性率（分别为40％、46％）高于Ⅲ～Ⅳ期者（分别为18％、18％）,两者分别比较,差异均有统计学意义（P值分别为0．018、0．004）。当联合分析TM4SF1、C1D、TIZ、FXR1基因的重组抗原的相应IgG型自身抗体及TIZ、FXR1基因的重组抗原的相应IgM型自身抗体（即自身抗体谱）时,诊断卵巢癌的敏感度为66％,准确度为73％;将该自身抗体谱与CA125联合时,敏感度、准确度均有明显提高,分别为83％、80％。结论SEREX技术与SSH方法相结合筛选肿瘤抗原基因是一种行之有效的、能筛选出具有较高特异性肿瘤抗原基因的研究策略;TM4SF1、C1D、TIZ、BARD1、FXR1、OV-189基因的重组抗原在血清中的相应自身抗体可作为卵巢癌诊断的标志物,多个抗原的联合检测可提高诊断效率。     

Surgery in ovarian cancer.

The role of surgery in the management of primary and recurrent ovarian cancer is reviewed. The data to support primary and secondary cytoreduction are summarized. The role of second-look surgery and of surgery in the palliation of ovarian cancer is also discussed.     

Familial ovarian cancer.

Familial ovarian cancer occurs in approximately 5% of all ovarian cancers. Since the relation between ovarian cancer and genetic heritage has drawn much attention lately, general gynaecologists will more and more be faced with the question how to survey patients from a family with the familial ovarian cancer syndrome. We describe a patient from a family with three daughters, of which two older sisters were known to have ovarian cancer. Although our patient was closely observed, a third-stage ovarian cancer developed. With this case in mind and after a review of the literature, we will in future closely survey patients from familial ovarian cancer families from their twentieth birthday on, and recommend prophylactic bilateral oophorectomy after child-bearing age. However, we are aware of the fact that it is impossible to diagnose ovarian cancer in a premalignant phase as yet, and the benefit of a close survey might be an earlier diagnosis and not prevention. Also, prophylactic oophorectomy does not prevent the occurrence of intra-abdominal malignancies histopathologically indistinguishable from ovarian cancer. Patients should be aware of these restrictions. If, in the future, the precise chromosomal defect in ovarian cancer families is localized, prevention of ovarian cancer, but not of intra-abdominal malignancies of the same histopathology, might be within reach.     

Familial ovarian cancer.

A family with epithelial ovarian carcinoma occurring in five members spanning three generations is presented. The pattern of appearance of the malignancies in this family is consistent with autosomal dominant transmission. The literature relating to familial ovarian cancer is reviewed and the management of women at risk for the development of ovarian cancer in these families is discussed.     

Therapeutic advances in ovarian cancer.

The propensity of ovarian cancer to recur--even after initial chemotherapeutic responses--is a problem that has been given a great deal of attention during the past year in the literature dealing with the treatment of ovarian cancer. Most of the articles address techniques to improve the percent of initial and secondary treatment responses. Several studies have described cytoreductive techniques to decrease the remaining tumor size for improved chemotherapeutic response. Cross-resistance between platinum analogues has been reconfirmed. However, improved secondary responses were seen when repeat treatment with platinum agents were preceded by a longer interval from initial platinum agent therapy. Radiation therapy has been shown to offer little solution to recurrent disease except possibly in a select group of patients with microscopic disease at second-look laparotomy. Reports on the use of carboplatin continue to demonstrate good initial responses, with decreased toxicity compared with cisplatin. Granisetron has been shown to significantly decrease the nausea and vomiting caused by emetogenic chemotherapy like cisplatin.     

应用抑制性消减杂交筛选卵巢癌紫杉醇耐药差异表达基因

目的:应用抑制性消减杂交技术研究人卵巢癌紫杉醇耐药细胞株OC3/Tax300与其亲本细胞OC3(敏感株)之间基因表达的差异,筛选耐药相关基因,探讨基因表达差异与卵巢癌耐药的相关性。方法:以卵巢癌紫杉醇耐药细胞株OC3/Tax300 mRNA为检测子(tester),以其亲本细胞OC3(敏感株)mRNA为驱赶子(driver),构建cDNA消减文库。随机挑取文库克隆测序,所得结果在GenBank中做同源性比较分析。结果:成功构建了卵巢癌紫杉醇耐药细胞株的特异性cDNA消减文库。从文库中选取阳性克隆,其中76个测序成功,再随机选取36个序列与GenBank数据库进行初步比对,8个可能为新基因,1个为蛋白序列,另27个来源于16个已知基因,这些差异表达基因主要涉及细胞代谢、信号转导、细胞骨架、凋亡、蛋白翻译合成、发育等相关基因。结论:部分基因表达差异与卵巢癌紫杉醇耐药有关。