The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass

ObjectiveThe purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malignant pelvis masses in Asian women.MethodsThis was a prospective, multicenter (n = 6) study with patients from six Asian countries. Patients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).ResultsA total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensitivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk.ConclusionROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.     

Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: Correlation with pathological outcome

ObjectiveThe quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease.MethodsThree hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample.ResultsMedian serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p < 0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p = 0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients.ConclusionsData presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.     

血清miR-222、HE4及CA125水平联合ROMA指数对上皮性卵巢癌的诊断价值

目的:探讨血清miR-222、血清人附睾蛋白4(HE4)及糖类抗原125(CA125)水平联合ROMA指数对上皮性卵巢癌(EOC)的诊断价值.方法:选取2016年1月至2019年12月海南西部中心医院收治的120例EOC患者、100例上皮性卵巢良性肿瘤患者和50例正常健康女性作为研究对象.实时定量PCR法检测miR-2...     

血清HE4和CA125联合检测预测盆腔包块患者卵巢癌的风险

目的:探讨新型肿瘤标记物人附睾分泌蛋白4(HE4)和CA125联合检测预测盆腔包块患者上皮性卵巢癌(EOC)风险的价值。方法:将诊断为盆腔包块拟行手术的患者纳入本研究。测定患者术前血清HE4和CA125水平,分别用绝经后和绝经前预测模型(ROMA)将患者划分至高危组和低危组,评估预测模型的应用价值。结果:评估了191例患者,其中138例盆腔良性疾病,53例盆腔恶性肿瘤,包括36例EOC。绝经后组盆腔良性疾病12例,8例划分至低危组,特异性66.7%(95%CI=40.0～93.3),恶性肿瘤37例,35例划分至高危组,敏感性94.6%(95%CI=87.0～101.9),EOC28例(含9例早期),全划分至高危组,敏感性100.0%。绝经前组良性疾病126例,103例划分至低危组,特异性81.7%(95%CI=75.0～88.5),16例恶性肿瘤,12例划分至高危组,敏感性75.0%(95%CI=54.0～96.2),EOC8例(含2例早期),全划分至高危组,敏感性100.0%。结论:ROMA成功地将盆腔恶性肿瘤患者划分至高危组,其中EOC患者全被正确地划分至高危组,可用于将恶性肿瘤患者尤其是EOC患者分流至有治疗经验的肿瘤医师及治疗中心。     

Combining clinical assessment and the Risk of Ovarian Malignancy Algorithm for the prediction of ovarian cancer

ObjectivesACOG guidelines for the evaluation of women with a pelvic mass employ a combination of physical exam, imaging, and CA125 to guide physicians in the triage of women to gynecologic oncologists. We studied the use of ROMA with clinical assessment for cancer risk assessment in women with a pelvic mass.MethodsThis was a prospective, multicenter trial evaluating women with a pelvic mass who had an initial clinical risk assessment (ICRA) performed by a generalist. ROMA scores were calculated and sensitivity, specificity, PPV and NPV were determined for ICRA and ICRA + ROMA.ResultsA total of 461 women were entered into the study. There were 375 benign tumors, 48 EOC, 18 LMP tumors and 20 non-ovarian malignancies. For detection of ovarian cancer alone, ICRA had a sensitivity of 85.4%, a specificity of 84.3%, and a NPV of 97.8%. Adding ROMA to ICRA produced a significant improvement of 8.4% in sensitivity, achieving a sensitivity of 93.8% with a specificity of 67.2% and a NPV of 98.8%. Examination of all malignancies (ovarian & non-ovarian) provided a sensitivity of 89.7% for ROMA + ICRA in comparison to 77.9% for ICRA alone, a significant increase in sensitivity of 11.8%. The NPV also significantly increased from 95.5% to 97.3%. Overall, ROMA detected 13 additional malignancies missed by ICRA.ConclusionsAdjunctive use of ROMA with clinical assessment improves the stratification of women with a pelvic mass into low and high risk groups for ovarian cancer. The combination is particularly effective in ruling out malignant disease.     

No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting

Objective

About 70% of epithelial ovarian cancer patients (EOC) are diagnosed at advanced stage with a five-year survival rate of only 30%. Whilst CA125 detects peritoneally-spread disease, it has limited sensitivity for early cancers, many of which are potentially curable.

Methods

We compared the new commercially available tumor marker HE4 with CA125 individually, in combination, within the risk of malignancy index (RMI) and the newly defined risk of malignancy algorithm (ROMA). Our prospectively-collected cohort of 160 patients consisted of healthy controls, benign diseases, and borderline tumors/adenocarcinomas of ovarian, tubal, peritoneal and endometrial origin. HE4 and CA125 were measured in serum using standardized ELISA.

Results

Both markers showed similar diagnostic performance in the detection of EOC at clinically defined thresholds (CA125 35 U/ml; HE4 70 pM) but HE4 was not elevated in endometriosis. Comparison of non-malignant diagnoses (n = 71) versus early stage ovarian and tubal cancers (n = 19) revealed that HE4 and ROMA displayed the best diagnostic performance (AUC 0.86/0.87, specificity 85.9%/87.3% and sensitivity 78.9%/78.9%, respectively). Whilst RMICA125 detects peritoneal cancer better than all other models (AUC 0.99, specificity 97.2%, sensitivity 80.0%), there is no other detection benefit from RMI compared to HE4 alone or included in ROMA.

Conclusions

The major advantage of HE4 lies in its specificity and improved detection of borderline tumors and early stage ovarian and tubal cancers. HE4 is superior to CA125 with or without RMI and ROMA indices. However, we see no benefit from combining both markers in clinical practice.     

Immunohistological analysis of stress-induced phosphoprotein 1 in ovarian cancer patients with low serum cancer antigen 125 levels

ObjectiveStress-induced phosphoprotein 1 (STIP1) was recently identified as a potential tumor marker for human ovarian cancer. This study further evaluates the usefulness of STIP1 in ovarian tumor patients with normal CA125 serum levels.Materials and MethodsSTIP1 and CA125 were immunohistochemically analyzed in 84 primary ovarian cancer and 30 benign ovarian tumors in patients with serum CA125 levels < 35 U/mL before surgery. Histoscores (0–300) were calculated as staining intensities (0–3) multiplied by percentage of tumor tissue (0–100%).ResultsThe cell types of the 84 cancers included 11 serous, 10 clear-cell, 51 mucinous, and 12 endometrioid carcinomas. There were 55 patients with invasive cancer and 29 with borderline ovarian tumors. The histoscores of STIP1, but not of CA125, in invasive cancer (mean ± SD, 186.3 ± 82.5) were significantly (p < 0.0001) higher than those seen in borderline ovarian tumors (86.2 ± 85.5). When the STIP1 histoscore was set at 183.8, invasive cancers (n = 55) were identified from benign tumors (n = 30) with a sensitivity of 56.4%, a specificity of 93.3%, a positive predictive value of 93.9%, and a negative predictive value of 53.8%. Results of receiver operating characteristics analysis showed that the area under curve of the STIP1 histoscore was 0.755, which was superior to that of CA125 (0.599).ConclusionSTIP1 histoscores may be useful in detecting invasive human ovarian cancer in patients with low serum CA125 levels.     

Serum arylesterase and paraoxonase activities in patients with ovarian tumors

ObjectiveHigh levels of toxic reactive oxygen species have been found in many types of cancer cells. Serum arylesterase (ARE) and paraoxonase (PON) are esterase enzymes that have strong antioxidant characteristics. The main purpose of our study was to evaluate the activity of ARE and PON in the sera of patients with ovarian cancer and benign ovarian tumors.Materials and methodsThis study included 30 patients with ovarian cancer, 42 patients with benign ovarian tumors, and 19 healthy age- and sex-matched individuals. ARE and PON activities were measured using spectrophotometry.ResultsSerum ARE activity was significantly different among the three studied groups (p < 0.0001). However, posthoc tests revealed that ARE activity was lower in the benign ovarian tumor group (median, 1.53 U/mL; range, 0.43–2.47 U/mL) than in the other groups. There were no differences in ARE activity between patients with ovarian cancer (1.89 U/mL; range, 1.01–2.56 U/mL) and healthy individuals (2.05 U/mL; range, 0.79–2.44 U/mL). We found no differences in PON activity or the PON:ARE activity ratio between the studied groups. Tumor size in the benign ovarian tumor group was positively correlated with ARE activity (R Spearman = 0.46, p = 0.003) and negatively correlated with PON activity (R Spearman = −0.50, p = 0.001). The ARE and PON activities were not influenced by histological type, ovarian cancer grade, or disease advancement.ConclusionARE activity is higher in patients with ovarian cancer than in patients with benign ovarian tumors; however, the serum activity of ARE is similar between patients with cancer and healthy individuals.     

IOTA SR 与 CA125、HE4、ROMA、RMI1、GI-RADS对卵巢良恶性肿瘤的诊断价值比较

目的 探讨糖链多肽抗原125(CA125)、人附睾蛋白4(HE4)、恶性肿瘤风险算法(ROMA)、恶性风险指数1(RMI1)、国际卵巢肿瘤分析简单规则(IOTA SR)、妇科影像报告与数据系统(GI-RADS)在卵巢良恶性肿瘤鉴别诊断中的价值.方法 选取2019年7 月至2020年7 月于锦州医科大学附属第一医院83例...     

Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass

Objective

Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes.

Methods

Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI.

Results

809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI = 200. The areas under the curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI).

Conclusion

HE4 and ROMA helps differentiating OC from other pelvic masses, even in early stage OC. ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.     

Brain metastasis from ovarian carcinoma: Analysis of eight cases from a single radiotherapy center

ObjectiveBrain metastasis from epithelial ovarian carcinoma (EOC) is rarely seen having rate of 1–3% with very poor prognosis. Studies on brain metastatic EOC is limited with low number of participants. An increasing trend in EOC related to brain metastasis has been reported recently confronting managing clinicians with new challenges. Therefore, more information on this issue is needed. We aimed to analyze a single radiotherapy center experience on EOC related brain metastases.Materials and methodsData of all patients treated between January 1998 and December 2016 at a radiation center of a university hospital were reviewed retrospectively. Clinicopathological characteristics, treatment details and outcome were analyzed.ResultsWe identified only ten cases with EOC related brain metastasis in our department during 18-year period. Two patients were excluded because of data unavailability and therefore our study was performed among 8 patients. The median time between EOC diagnosis and detection of brain metastasis was 19.8 months. Brain metastasis was multiple in majority (75%). Extracranial metastasis at the time of brain metastasis was 62.5%. All patients died in the follow-up. The median survival time after the diagnosis of brain metastasis was 4.5 months. The median overall survival (OS) after the diagnosis of EOC was 28.9 months. The interval between the initial diagnosis and brain metastasis was negatively correlated with survival after brain metastasis (B-OS) occurred as time interval (p = 0.047). Presence of extracranial metastasis at time of occurrence of brain metastasis and application of multimodal treatment after brain metastasis were positively correlated with B-OS time (p = 0.007, p = 0.046, respectively).ConclusionPrognosis of brain metastasis from EOC remains poor. The factors associated with better B-OS were the longer time between initial diagnosis and brain metastasis, absence of extracranial disease at time of brain metastasis, and application of the multimodal treatment.     

The safety and feasibility of no-placement of urinary catheter after single-port laparoscopic surgery in patients with benign ovarian tumor: A retrospective cohort study

ObjectiveThe aim of this study was to investigate the feasibility and safety of no placement of urinary catheter after single-port laparoscopic surgery in patients with benign ovarian tumor.Materials and MethodsPatients with benign ovarian tumor who received ovarian cystectomy or oophorectomy via single-port laparoscopic surgery in our department were screened between July 2019 and March 2021. Patients were divided into placement of urinary catheter group or no-placement of urinary catheter group according to whether an indwelling catheter was used after single-port laparoscopic surgery, and length of hospital stay, occurrence of postoperative urinary retention, incidence of urinary tract infection and re-insertion rate of urinary catheters were compared.ResultsThere was no significant difference in the rate of urinary catheter re-insertion between the two groups (P = 0.431), but a higher incidence of urinary catheter re-insertion was found in the group of dwelling urinary catheter placement. Simultaneously, there were no significant differences in the rates of urinary tract infection and postoperative urinary retention (1.6% vs 0.6%; P = 0.391 and 4.3% vs 6.9%; P = 0.295, respectively) between the two groups, whereas a significant shorter length of hospital stay was observed in the non-urinary catheter group when compared to the urinary catheter group (4.61 ± 1.40 vs 5.23 ± 1.72; p < 0.001).ConclusionsOur retrospective study provided evidence to the hypothesis that no placement of urinary catheter in patients with benign ovarian tumor was safe and feasible after single-port laparoscopic surgery. Meanwhile, avoiding urinary catheter could contributed to decrease in the length of hospital stay and is conducive to the enhanced recovery of patients.     

Impact of neoadjuvant chemotherapy cycles prior to interval surgery in patients with advanced epithelial ovarian cancer

Objectives

Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients.

Methods

Data from EOC patients (stages IIIC–IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (< 4 = group B1; > 4 = group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed.

Results

367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p < 0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p < 0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p < 0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p < 0.001)) with an independent impact from disease stage and WHO performance status.

Conclusions

Patients with advanced EOC receiving complete IDS after more than 4 cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC.     

Defective expression of Protein 4.1N is correlated to tumor progression,aggressive behaviors and chemotherapy resistance in epithelial ovarian cancer

Objective

Protein 4.1N (4.1N) is a member of the Protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. In this study, we evaluated the expression of 4.1N protein and its potential roles in epithelial ovarian cancer (EOC) tumorigenesis and progression.

Methods

4.1N protein expression was investigated in a total of 280 samples including 74 normal tissues, 35 benign, 30 borderline and 141 malignant epithelial ovarian tumors by immunohistochemistry. Correlation between 4.1N expression levels and clinicopathologic features was statistically analyzed. The expression of 4.1N in EOC cell lines was examined by western blotting.

Results

Immunohistochemistry analysis revealed that, although there was no loss of 4.1N expression in normal tissues and benign tumors, absence of Protein 4.1N was significantly more common in EOCs (44.0%) than in borderline tumors (3.3%) (p < 0.001). Furthermore, loss or decreased expression of 4.1N protein expression was correlated with malignant potential of the tumors (14.3% in benign tumors, 56.7% in borderline tumors and 92.9% in malignancy) (p < 0.001). In EOC samples, loss of 4.1N protein was significantly associated with advanced-stage (p = 0.004), ascites (p = 0.009), omental metastasis (p = 0.018), suboptimal debulking (p = 0.024), poorly histological differentiation (p = 0.009), high-grade serous carcinoma (p = 0.001), short progression-free-survival (p = 0.018) and poor chemosensitivity to first-line chemotherapy (p = 0.029). Moreover, western blotting analysis revealed that expression of 4.1N protein was lost in 4/8 (50%) EOC cell lines.

Conclusions

4.1N protein expression level was significantly decreased during malignant transformation of epithelial ovarian tumors and that loss of 4.1N expression was closely correlated to poorly differentiated and biologically aggressive EOCs.     

Global methylation profiling in serous ovarian cancer is indicative for distinct aberrant DNA methylation signatures associated with tumor aggressiveness and disease progression

ObjectiveTo characterize at high resolution the DNA methylation changes which occur in the genome of serous epithelial ovarian cancer (EOC) in association with tumor aggressiveness.MethodsMethylated DNA immunoprecipitation in combination with CpG island-tiling arrays was used to compare the methylation profiles of five borderline, five grade 1/stage III/IV, five grade 3/stage I and five grade 3/stage III/IV serous EOC tumors, to those of five normal human ovarian tissue samples.ResultsWe found widespread DNA hypermethylation that occurs even in low-malignant potential (borderline) tumors and which predominantly includes key developmental/homeobox genes. Contrary to DNA hypermethylation, significant DNA hypomethylation was observed only in grade 3 serous EOC tumors. The latter observation was further confirmed when comparing the DNA methylation profiles of primary cell cultures derived from matched tumor samples obtained prior to, and following chemotherapy treatment from two serous EOC patients with advanced disease. To our knowledge this is the first report that has shown the presence of massive DNA hypomethylation in advanced serous EOC, associated with tumor malignancy and disease progression.ConclusionsOur data raise the concern that demethylating drugs that are currently being used in advanced EOC disease (representing the majority of serous EOC cases) might have adverse effects due to activation of oncogenes and prometastatic genes. Understanding the relative roles of hypomethylation and hypermethylation in cancer could have clear implications on the therapeutic use of agents targeting the DNA methylation machinery.     

Prognostic value of lymph node ratio in patients with advanced epithelial ovarian cancer

ObjectiveLymph node status is an established prognostic factor in epithelial ovarian cancer (EOC). Lymph node ratio (number of positive LN/number of resected LN) reflects both qualitative and quantitative lymph node spread as well as surgical effort and extent of disease. We evaluated whether LNR is a more precise prognostic factor than conventional lymph node status in patients with EOC.MethodsThe present retrospective study includes 809 patients with EOC, who underwent primary cytoreductive surgery between 2000–2013. Clinico-pathological parameters and survival data were extracted from a prospectively maintained tumor registry database. The optimal cut-off point for LNR was calculated by using Martingale residuals. Survival analyses were calculated using Kaplan–Meier method and Cox regression models.ResultsLymphadenectomy was performed in 693 (85.7%) out of 809 patients. Median number of removed LN was 64 (IQR 25–75%: 39–84). LNR of 0.25 was identified as the optimal prognostic cut-off value. The estimated 5-year-OS rates were 69.3% for patients with node-negative EOC compared to 33.1% for patients with any lymph node metastasis (p < 0.001). The estimated 5-year-OS rates were 42.5% for patients with LNR ≤ 0.25, and 18.0% for patients with LNR > 0.25 (p < 0.001). Additionally in multivariate analysis LNR > 0.25 was approved to be an independent prognostic factor for overall survival (adjusted HR 1.44, 95% CI 1.04–2.00; p = 0.028).ConclusionLNR more precisely predicts overall survival than conventional lymph node status in EOC patients undergoing primary debulking surgery.     

Luteinizing hormone in peritoneal and ovarian cyst fluids: a predictor of ovarian carcinoma

Objective: The aim of this study was to define the role of luteinizing hormone (LH) as a tumor marker, specific for ovarian cancer. Methods: The study included 34 women with functional and benign ovarian cysts, 11 women with borderline ovarian tumors, 22 patients with advanced ovarian cancer and 15 patients with non-ovarian intraperitoneal malignancies. Serum, peritoneal fluid and ovarian cyst aspirates were obtained intraoperatively (laparoscopy or laparotomy) and were subjected to the LH analysis. Results: Peritoneal fluid LH levels were significantly increased in patients with ovarian cancer and those with borderline ovarian tumors as compared to patients with functional and benign ovarian cysts (P=0.005 and P=0.007, respectively). The patients with non-ovarian malignancies demonstrated the same peritoneal fluid LH levels as patients with benign ovarian tumors. There was no significant difference in the level of peritoneal fluid LH between ovarian cancer patients with and without ascites. The patients with functional and benign ovarian cysts demonstrated also significantly lower cyst fluid LH levels as compared to patients with malignant and borderline ovarian cysts (P=0.01 and P=0.03, respectively). Peritoneal and ovarian cyst fluid levels of LH were significantly increased in patients with fibrothecomas as compared to patients with other benign ovarian cysts. There were no significant differences in the serum LH levels comparing patients from all study groups. Conclusion: LH, detectable in peritoneal and ovarian cyst fluids, can be used as a tumor marker for identification of patients with borderline and malignant ovarian tumors.     

TrkB及其配体BDNF在卵巢上皮癌中的表达及其临床意义

目的检测酪氨酸激酶B（tyrosine kinase,TrkB）及其配体脑源性神经营养因子（brainderived neurotrophic factor,BDNF）在卵巢上皮癌（EOC）中的表达,并探讨其临床意义。方法选择中山大学附属肿瘤医院病理存档的石蜡标本108例,其中10例正常卵巢、17例良性卵巢肿瘤、21例卵巢交界性肿瘤和60例卵巢上皮癌,采用免疫组化链霉素抗生物素蛋白-过氧化物酶法（SP法）检测TrkB及其配体BDNF蛋白的表达水平,分析其与临床病理因素之间的关系。结果 TrkB和BDNF蛋白在正常卵巢组织和良性卵巢上皮性肿瘤中无表达;在交界性和卵巢上皮性癌中的阳性表达率分别为19.0%、71.7%和14.0%、51.7%（P〈0.05）。TrkB和BDNF蛋白在EOC组中的表达水平与其FIGO分期及病理分级有关,在Ⅲ期＋Ⅳ期、低分化组（G3）比Ⅰ期＋Ⅱ期、高中分化（G1、G2）组表达率高（P〈0.05）。TrkB和BDNF在卵巢上皮癌中的表达水平呈正相关（r=0.428,P〈0.05）。结论卵巢上皮癌中存在TrkB和BDNF的异常高表达。TrkB和BDNF可能协同作用促进了卵巢上皮癌的发生、发展,并有望成为卵巢上皮癌基因治疗的新靶点。     

Impact of young age on platinum response in women with epithelial ovarian cancer: Results of a large single-institution registry

ObjectiveIn young women, EOC is a rare disease with an uncertain genetic and biological substrate.MethodsWe report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30 years to randomly selected older patients aged ≥40 years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures.ResultsEOC was diagnosed in 68 patients aged ≤30 years matched with 111 patients aged ≥40 years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n = 35) and mucinous (i.e. 23%, n = 16 infiltrative and 12% n = 8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n = 5). Early stage diseases (53%, n = 36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p = 0.0002). For HG tumors the PFS is of 0% at 5 and 10 years in younger as compared to 30% in older patients. No difference in PFS (median 4.9 vs 9.8 ms, p = 0.58) and OS (not reached vs 15.3 ms, p = 0.47) is found overall among younger and older patients respectively. The median follow-up was 72 months (range, 11–288 months). No genetic abnormalities were found.ConclusionsYoung EOC patients are most often diagnosed at an early FIGO stage with LG serous or mucinous histology. Tumors are significantly more resistant to platinum-based chemotherapy in younger patients.     

eIF-4E、OPN在上皮性卵巢癌患者血清中的表达及临床意义

目的:检测eIF-4E、OPN在上皮性卵巢癌患者血清中的表达,探讨eIF-4E、OPN作为肿瘤标志物,与CA125联合检测的临床意义。方法:采集卵巢上皮性癌46例,卵巢交界性上皮性肿瘤16例、卵巢良性上皮性肿瘤12例及健康妇女12例的血清标本,用双抗体夹心(ELISA)法检测血清标本中eIF-4E、OPN的浓度,血清CA125浓度用化学发光法检测。结果:卵巢恶性肿瘤组及交界性肿瘤组血清中eIF-4E、OPN、CA125的浓度明显高于卵巢良性肿瘤组及正常对照组。eIF-4E检测阳性率63.04%,OPN检测阳性率76.9%,CA125检测阳性率71.74%,eIF-4E和CA125联合检测阳性率93.48%,OPN和CA125联合检测阳性率89.13%,eIF-4E、OPN及CA125三者联合检测阳性率97.83%。Ⅲ、Ⅳ期卵巢癌患者血清中CA125、eIF-4E、OPN浓度明显高于Ⅰ、Ⅱ期。结论:eIF-4E、OPN可作为卵巢肿瘤标志物,用于卵巢癌早期诊断,与CA125联合检测有较高的临床应用价值。