What should be the cut-off level of serum CA125 to evaluate the disease status before second-look laparotomy in epithelial ovarian carcinoma?

To assess the predictive value of serum CA125 level prior to second-look laparotomy in epithelial ovarian carcinoma, 45 patients who were clinically or radiologically tumor-free prior to a second-look laparotomy were studied. Serum CA125 levels were measured 10 days prior to the operation, and were compared with the surgico-pathological results. Twenty-eight (62%) patients were found to have tumor at surgery. The serum CA125 levels were  35 U ml⁻¹ (42%) patients. Tumors were found in 14 (74%) of these 19 patients. Although a serum CA125 level  35 U ml⁻¹ was a strong predictor of the presence of an intraperitoneal tumor, a level <35 U ml⁻¹ was not predictive of a tumor-free state. When the cut-off level was accepted as 20 U ml⁻¹, 28 patients (62%) were found to have elevated CA125 level. The sensitivity, the specificity, the positive and negative predictive value and the false negative ratio were calculated as 79%, 65%, 79%, 65% and 21% respectively. The threshold value for a raised CA125 level was considered and a lower level of 20 U ml⁻¹ was suggested as a cut-off level prior to second-look laparotomy in evaluating patients with known epithelial ovarian cancer.     

Serum CA 125 as a tumor marker and the expression of c-erbB-2 oncogene in tubal malignancies

Serum CA 125 levels were evaluated in 26 patients with fallopian tube malignancies. CA 125 was elevated preoperatively in seven samples (median 178 U ml⁻¹ range 41–19021 U ml⁻¹), and postoperatively in eight of nine (89%) samples collected from patients with residual disease (median 109 U ml⁻¹ range 10–1883 U ml⁻¹) but only in one of seven (14%) samples from patients without residual disease (median 14, range 5–170 U ml⁻¹) ( P < 0.001). Changes in the serum CA 125 level during chemotherapy correlated with the clinical course of disease in 13 of 14 patients with a pre-chemotherapy serum CA 125 level> 35 U ml⁻¹. Nine patients with clinical remissions showed decreasing serum CA 125 levels, one with clinically stable disease showed decreasing levels and four with disease progression showed increasing levels. Serum CA 125 levels were measured in four patients before second-look laparotomy. Two of three with positive findings at laparotomy had elevated serum CA 125 levels whilst the third had a normal level. One patient with negative findings at second-look surgery had a normal CA 125 level. Disease relapse was associated with elevated serum CA 125 levels in nine of 10 patients (median 108 U ml⁻¹, range 27–38200 U ml⁻¹). Using immunohistochemical staining, none of the tumors showed positive cytoplasmic staining for c-erbB-2 (NEU) oncogene. This report shows that CA 125 is a reliable tumor marker for monitoring patients with cancer of the fallopian tube during active treatment and follow-up.     

Serum CA125 assay at the time of relapse has no prognostic relevance in patients undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian study

The present retrospective study assessed the prognostic value of serum CA125 assay at relapse in 73 patients with recurrent epithelial ovarian cancer. At the time of relapse, serum CA125 levels ranged from 7 to 7000 U ml⁻¹. The 25%, 50% and 75% quantiles of CA125 levels were 76, 178 and 339 U ml⁻¹, respectively. Antigen values were >35 U ml⁻¹ in 67 (91.8%) of the 73 patients. Median time to recurrence was 16 months (range, 4–62 months). Serum CA125 levels at relapse were not related to site of recurrence, time to recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. Sixty patients received salvage chemotherapy at relapse. In these patients survival after recurrence was significantly related to time to recurrence ( 6 months vs < 6 months, P  = 0.0371; 12 months vs >12 months, P  = 0.0014; 16 months vs >16 months, P = 0.0001), but not to CA125 level at relapse (at any cut-off value for the antigen: 35, 76, 178 and 339 U ml⁻¹ ), site of recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. In conclusion, time to recurrence was the only variable predictive of further survival in patients undergoing salvage chemotherapy for recurrent ovarian cancer, whereas serum CA125 level at relapse had no prognostic relevance.     

Preoperative discrimination between ovarian carcinoma, non-ovarian gynecological malignancy and benign adnexal masses using serum levels of CA125 and the polymorphic epithelial mucin antigens CASA, OSA and MSA

Serum levels of the tumor associated antigens CA125, CASA, OSA and MSA were determined preoperatively in a non-consecutive series of patients with: invasive epithelial ovarian cancer (OC, n = 87), ovarian tumors of low malignant potential (LMP, n = 9), benign adnexal masses (BAM, n = 48) and other peritoneal and pelvic malignancies ( n = 48). In addition, serum levels of CASA, OSA, and MSA were determined in 3477 asymptomatic well women. Ninety-eight percent of the asymptomatic women had CASA levels < 6.0 U ml⁻¹, OSA levels < 5.5 U ml⁻¹ and MSA levels < 80.0 U ml⁻¹. Serum CA125 levels were> 35 U ml⁻¹ in 89% of OC, in 44% of LMP, and in 23% of BAM. Serum CASA levels were> 6.0 U ml⁻¹ in 58% of OC, in 0% of LMP, and in 0% of BAM. Serum OSA levels were> 5.5 U ml⁻¹ in 61% of OC in 0% of LMP and in 4% of BAM. Serum MSA levels were> 80.0 U ml⁻¹ in 56% of OC, in 11% of LMP, and in 10% of BAM. When cut-off levels were set to exclude all patients with BAM, the best discrimination from OC using a single assay was achieved using CASA (58%). However, a combination of CASA and CA125 gave positive levels in 69% of OC at levels which precluded BAM. All markers were also elevated in some colon cancers, cervical cancers, uterine cancers and other peritoneal malignancies. A combination of CA125 and CASA levels, obtained preoperatively may assist the general gynecologist in avoiding potentially difficult oncologic surgery.     

Evaluation of serum CA 125 level as a tumor marker in borderline tumors of the ovary

Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20 (90%) samples (median 66, range 5–272 U ml⁻¹). Preoperative serum CA 125 levels did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated in seven of nine (78%) with serous tumors (median 131, range 5–272 U ml⁻¹) and in all 11 with mucinous tumors (median 62, range 41–157 U ml⁻¹). There was no significant difference in the CA 125 levels between these two histologic types. Postoperative serum CA 125 levels, measured 3–6 weeks after primary laparotomy, were significantly lower than the preoperative ones ( P < 0.001). No difference in the postoperative CA 125 levels was found between those with and those without residual disease after surgery. Postoperative serum CA 125 levels were elevated in eight of 60 (13%) without residual tumor. None of these had relapsed at the time of analysis (26–87 months after surgery). Serum CA 125 levels tended to correlate with disease evolution during chemotherapy. Two with disease remissions had falling levels, one with stable disease had falling level and one with disease progression had rising level. Serum CA 125 samples were obtained before second-look laparotomy in seven patients. Two with negative findings at second-look had normal levels. Of five with positive findings at laparotomy only two had elevated serum CA 125 levels. Disease relapse was associated with elevated serum CA 125 levels in only one of six patients.     

CA 125 measurements in ovarian cancer patients during their first postoperative week

Cancer antigen 125 (CA 125) was measured in 17 patients with ovarian carcinoma before their primary operation and during the first week after surgery. The purpose was to correlate the change in the antigen level with the patient's survival. Before surgery normal (16–30 U ml⁻¹ CA 125 values were measured in four patients and 13 had increased (75–11.356 U ml⁻¹) antigen concentrations. After surgery the marker increased to 104–931% of the preoperative level in five patients. In 12 patients the post-operative antigen level decreased to 20–96% of the preoperative level. In seven of these patients CA 125 increased without exceeding the preoperative level, after the initial postoperative fall. Thus, the CA 125 level during the first week after primary operation of ovarian cancer patients seems to be influenced by other variable factors besides a reduced amount of tumor tissue. Therefore, an investigation of the correlation between the change in the CA 125 concentration within the first week after surgery and the survival of the patient cannot be performed for the time being.     

An assessment of peritoneal lavage fluid CA125 as a tumor marker in epithelial ovarian cancer

Abstract. Redman CWE, Blackledge G, Luesley DM, Lawton FG, Kelly K, Chan KK. An assessment of peritoneal lavage fluid CA125 as a tumor marker in epithelial ovarian cancer, Int J Gynecol Cancer 1991; 1: 215–222.
CA125 levels in peritoneal lavage fluid (PLF) has been evaluated as a tumor marker in EOC. PLF samples were obtained by performing peritoneal lavage with 1L 0.9% saline, usually via temporary percutaneous cannulae. The study group comprised 87 EOC and 40 control patients; in controls, peritoneal lavage was performed at laparoscopy. Repeated access was associated with significant problems which curtails the potential of IP monitoring. Overall 25% of peritoneal lavage attempts were unsuccessful. A normal upper limit of 60 U ml⁻¹ was established for PLF CA125. In patients with postoperative disease, pre-treatment PLF and serum CA125 (using a cut-off point of 30 U ml⁻¹) levels were elevated in 66 and 87% of cases, respectively. PLF CA125 had a stronger association with the presence of ascites than with the amount of residual disease. PLF CA125 levels correlated with observed response in 71% of 51 patients with evaluable response, which was not significantly less than the 83% observed for serum CA125. Serial measurement demonstrated that rising PLF CA125 levels can predict relapse but that serum CA125 was at least as good in this respect. PLF CA125 is not a more sensitive tumor marker than its serum counterpart and will contribute little to the management of EOC.     

CA 125 in serum and tumor from patients with uterine sarcoma

Serial serum samples of 33 patients with primary sarcoma of the uterus were analyzed for CA 125 and frozen tissue sections of tumor from 23 patients were tested for this antigen. Before treatment, 12 of 30 evaluable patients showed serum CA 125 levels> 16 Uml⁻¹ (40%). There was no relationship between serum CA 125 level and the histologic subtype. Patients with serum CA 125> 16 Uml⁻¹ showed extrauterine tumor sites in 67% of the cases versus 33% in patients with normal CA 125 determinations ( P = 0.026). In (FIGO) stages I and II, elevated serum CA 125 levels prior to surgery were associated with a poor prognosis ( P = 0.043). Patients with recurrent or progressive disease demonstrated serum CA 125 levels> 16 Uml⁻¹ in 14 of the 20 cases (70%). Sarcoma cells were completely negative for CA 125, whereas positivity was observed in the epithelial component of mixed Müllerian tumors. The source of the elevated serum CA 125 levels in patients with uterine sarcoma may be stimulated mesothelial cells.     

Monitoring patients with ovarian carcinoma: the relationship of serum CA125 levels to CT scanning

Abstract. The serial levels of the serum tumor marker CA125 were compared with the results of concurrent abdominopelvic CT scans throughout the clinical course of 65 patients undergoing treatment for advanced epithelial ovarian carcinoma at this institution. Twenty-three of these patients subsequently underwent a second laparotomy following chemotherapy, and the pathological findings were correlated with the preoperative results of both the serum CA125 levels and CT scan appearances in order to establish the relative accuracies of the two tests in the diagnosis of residual disease. Initially, all patients had an elevated CA125 level (< 400 units ml^-1) which fell to normal following treatment in all cases. Seventy-five percent of patients showed continuing evidence of disease on CT grounds when both clinical examination and serum CA125 levels had normalized during or following treatment. Patients whose maximum response was PR on CT criteria relapsed faster than those achieving CR, showing CT to be a useful indicator of residual disease when the CA125 level has normalized after chemotherapy. Comparing the CT results and CA125 levels after second-look surgery in 23 patients showed CT to have a sensitivity of 85% and specificity of 42%; CA125 had a sensitivity of 50% with a specificity of 100%. Using this data, a protocol for monitoring patients undergoing treatment and follow-up for ovarian carcinoma is suggested.     

Significance of CA 125 serum level in discrimination between benign and malignant masses in the pelvis

Aim Our aim was to confirm that preoperative CA 125 serum level can be useful for discrimination between benign and malignant masses in the pelvis.Methods Preoperative CA 125 serum level was analyzed retrospectively in 121 patients who had surgery because of a malignant ovarian tumor and in 91 patients with benign masses in the pelvis. The cutoff serum level CA 125 between benign and malignant masses in the pelvis was 35 and 65 IU/ml.Results Of those patients with a malignant ovarian tumor, 65.3% had menopause whereas only 31.5% of those with a benign tumor did so. The average age of the patients with a malignant tumor was 54.2 years and of those with a benign tumor 46.8 years. The preoperative CA 125 serum level was higher than 35 IU/ml in 80.2% and higher than 65 IU/ml in 72.7% of all analyzed patients with a malignant tumor, whereas it was 23.9% and 9.8% respectively in patients with a benign mass. In early stage ovarian cancer disease (borderline stage, I/II) the preoperative CA 125 serum level was higher than 35 IU/ml in 67.8% and in 52.5% higher than 65 IU/ml. In advanced stages (III/IV), it was higher than 35 and 65 IU/ml in 96.1%. After therapy the CA 125 serum level dropped below 35 IU/ml in 70.8% and after three chemotherapy courses in 78.1%. A CA 125 level less than 35 IU/ml was achieved by therapy in 84.2% patients with an early stage disease (I/II) and in 62.1% in advanced stages (III/IV). The calculated sensitivity was 80.2% and negative 74.5% (CA 125 higher than 35 IU/ml) and 72.7%, 90.2%, 90.7%, 71.6% respectively (CA 125 higher than 65 IU/ml).Conclusion Preoperative determination of CA 125 is a very useful method to discriminate between benign and malignant masses in the pelvis.     

人附睾分泌蛋白4联合CA125在卵巢恶性肿瘤与子宫内膜异位症鉴别诊断中的价值

目的 探讨血清人附睾分泌蛋白4(HE4)联合CA125水平检测在卵巢恶性肿瘤与子宫内膜异位症鉴别诊断中的价值.方法 采用酶联免疫吸附试验(ELISA)检测卵巢子宫内膜异位囊肿(内异症组)46例、卵巢上皮性癌(卵巢癌组)36例、卵巢非内膜异位良性肿瘤(良性肿瘤组)60例和健康妇女(对照组)50例血清中HE4和CA125水平,结果以中位数表示.血清HFA和CA125正常值分别为0～150 pmo/L和0～35 kU/L,单独或联合检测时,其中任一指标高于正常上限即定为阳性.通过制作受试者工作特征(ROC)曲线,以曲线下面积(AUC)反映诊断的准确性;以Mann-Whitney U 检验及相关性分析探讨两项指标单独或联合检测用于诊断卵巢内异症囊肿的价值.结果 (1)HE4水平:内异症、对照、良性肿瘤组妇女血清HE4水平分别为52.4、51.0、50.0 pmoL/L,3组比较,差异无统计学意义(P>0.05),卵巢癌组患者HE4水平为507.5 pmoL/L,与其他3组分别比较,差异均有统计学意义(P<0.05).(2)CA125水平:卵巢癌、内异症、良性肿瘤及对照组妇女血清CA125水平分别为743.0、84.9、15.4、11.5 kU/L,卵巢癌组与其他3组比较,差异均有统计学意义(P<0.05).(3)单项榆测结果:卵巢癌组以内异症组为参照时,HE4和CA125笛单项检测的AUC分别0.933和0.821,其特异度为95%时的敏感度分别为79.6%和49.0%;内异症组以对照组为参照时的AUC为0.453;以良性肿瘤组为参照时的AUC为0.496.(4)联合检测结果:卵巢癌组以内异症组为参照时,HE4联合CA125检测的AUC为0.936,其特异度为95%时的敏感度为81.0%.结论 HE4水平可作为卵巢内异症囊肿的鉴别诊断依据之一,HE4联合CA125水平检测能有效鉴别卵巢内异症囊肿和卵巢恶性肿瘤.     

Serum CA 125 concentrations in women of different ages, hormonal statuses, orclinical conditions

Koper NP, Thomas CMG, Massuger LFAG, van der Mooren MJ, Kiemeney LALM,Verbeek ALM. Serum CA 125 concentrations in women of different ages, hormonalstatuses, or clinical conditions. Int J Gynecol Cancer . 1997; 7 : 405–411.
Changes in serum cancer antigen (CA) 125 concentrations during the normalmenstrual cycle, the suppressed or stimulated cycle, pregnancy, and duringhormone replacement therapy (HRT) after menopause were studied to gain abetter understanding of factors that influence serum CA 125 concentrations.The clinical status of 300 women was reviewed and their serum CA 125concentration was determined. In the normal-cycle group and in the oralcontraceptive group CA 125 serum concentrations were higher during the early (follicular) phaseof the menstrual cycle than during the later (luteal) phase. No increase inserum CA 125 concentration was seen in the ovarian stimulation group. Serum CA125 concentrations were higher in the first trimester of pregnancy. In both groupsof postmenopausal women mean serum CA 125 concentrations were below 10 Uml⁻¹. During HRT, serum CA 125 concentrations increased inthe non-hysterectomy group while a decrease was seen in the hysterectomygroup. Ovarian activity is of limited influence on the serum CA 125concentration. Changes taking place within the endometrial tissue may be ofmore importance. The low serum CA 125 concentrations observed in the groupsof postmenopausal women suggest that it may be justified to employ lowerreference values for serum CA 125 in the clinical management and follow-up ofovarian cancer patients.     

Combination assay of CA125, TPA, IAP, CEA, and ferritin in serum for ovarian cancer

The levels of CA125, TPA, IAP, CEA, and ferritin in the serum were measured simultaneously in 68 healthy nonpregnant females and 133 patients with various gynecological diseases, and were subjected to statistical discriminant analysis for the diagnosis of ovarian cancer. The usefulness and the limits for diagnosis of various gynecological diseases were investigated for each tumor marker. Also, the diagnostic usefulness of the stepwise discriminant analysis employing the values of these five tumor markers in the serum in cases of ovarian cancer was compared with that of CA125 measurements alone. Because the frequency of cases with an elevated serum CA125 level increased more specifically in the ovarian cancer group than those of other tumor makers in the serum, this parameter was considered to be more useful for the diagnosis of ovarian cancer than the levels of the other tumor markers. The frequencies of cases with the elevated serum CA125 levels, however, also increased in the groups of patients with endometriosis and at an early stage of normal pregnancy more than in the group of healthy nonpregnant females. In the ovarian cancer patients, the discriminant analysis employing the values of CA125 and four other tumor markers in sera was more useful for early diagnosis, differential diagnosis, early detection of recurrences, and the determination of complete remission after therapy than the measurement of the serum CA125 level alone.     

Metastatic colorectal adenocarcinoma involving the ovary with elevated serum CA125: a potential diagnostic pitfall

OBJECTIVES: Elevated serum levels of CA125 are observed not only in association with primary ovarian epithelial neoplasms but also in a variety of other clinical settings, including ovarian involvement by metastatic disease. There is considerable overlap in gross and histologic features between primary ovarian tumors and metastatic colorectal adenocarcinoma, which can make diagnosis particularly challenging in the setting of an increased CA125 level. The aims of this study were to determine how frequently serum CA125 is elevated in women with ovarian involvement by metastatic colorectal adenocarcinoma and to compare the features of cases with and without associated elevations of serum CA125. METHODS: Eighty-nine cases of histologically confirmed ovarian involvement by metastatic colorectal adenocarcinoma were identified by retrospective review. Clinicopathologic data were analyzed, including preoperative serum CA125 level (available in 42 cases). Features of cases with an associated increase in serum CA125 were compared with those of cases with no such elevation. RESULTS: Twenty-nine patients had an elevated serum CA125 level (>35 U/mL) preoperatively (range 39.0-556.3, median 143.0, mean 199.1). Thirteen patients had a serum CA125 level within the reference range, while forty-seven patients had no preoperative testing for serum CA125. Clinical, gross, and histologic features of cases with an associated increase in serum CA125 were generally similar to those of cases with a non-elevated serum CA125 concentration. In three cases, the tumor was initially diagnosed as an ovarian primary. CONCLUSIONS: At least 32.6% of women with ovarian involvement by metastatic colorectal adenocarcinoma have an elevated serum CA125 level prior to oophorectomy. Such cases do not differ significantly from cases lacking such an association with respect to a variety of clinicopathologic features. The possibility of metastasis from a colorectal carcinoma merits consideration in the formation of the differential diagnosis for a woman with an adnexal mass and elevated serum CA125, even in the absence of an established history of gastrointestinal malignancy.     

Screening for ovarian cancer using serum CA125 and vaginal examination: report on 2550 females

This study was undertaken to assess the effectiveness of using serum CA125 and vaginal examination as a screening test for ovarian cancer in apparently healthy females. Two thousand five hundred and fifty healthy females aged 40 and over were recruited to participate in a screening study involving a questionnaire, serum CA125 measurement and vaginal examination. Females with either an elevated CA125 level or abnormal vaginal examination had a pelvic ultrasound performed as a secondary procedure. The positive predictive values of an elevated serum CA125 level, and a combination of CA125 level measurement and vaginal examination for ovarian cancer, were 1/100 and 1/3, respectively. The specificities of serum CA125 levels, vaginal examination and both in combination were 96.1%, 98.5% and 99.9%, respectively. In postmenopausal females the positive predictive values were improved with CA125 measurement alone, giving a positive predictive value of 1/24. Seventeen females underwent operative procedure as a result of the screening—only one of these was for an ovarian cancer. The combination of serum CA125 measurement and vaginal examination is not an effective screening test in the general population, although in postmenopausal females it does achieve acceptable specificities and positive predictive values.     

Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma

OBJECTIVES: The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas. Because these elevations may precede clinical detection by a year or more, CA 125 is potentially useful for early detection as part of an ovarian cancer screening program. However, CA 125 is often not elevated in clinically detected cancer and is frequently elevated in women with benign ovarian tumors. CA 125 may be more useful in conjunction with one or more other tumor biomarkers. Additional markers could play a role if, when used with CA 125, they identify some carcinomas missed by CA 125 (i.e., they improve sensitivity), rule out false positives (i.e., improve specificity), or are able to detect the same cancers earlier. METHODS: We have evaluated a composite marker (CM) that combines CA 125 and a previously described soluble mesothelin related (SMR) marker in sera from 52 ovarian cancer cases, 43 controls with benign ovarian tumors, and 220 normal risk controls who participated in a screening program, including 25 healthy women having two serum samples collected 1 year apart. CA 125, SMR, and CM were evaluated for their ability to identify clinical disease and for their temporal stability, which assesses their ability to obtain even greater sensitivity when used in a longitudinal screening program. RESULTS: CM has the best sensitivity, with specificity equal to CA 125. Importantly, CM has temporal stability at least as high as CA 125. CONCLUSION: The CM may outperform CA 125 alone in a longitudinal screening program as well as in a diagnostic setting.     

CA125 expression in spontaneous ovarian adenocarcinomas from laying hens

OBJECTIVE: Currently, there is not a fully characterized model for human ovarian cancer; however, 2- to 4-year-old laying hens spontaneously develop ovarian tumors. CA125 expression is a hallmark of ovarian cancer in women. The major objective of this study was to characterize the in vitro growth of avian ovarian tumor cells, and CA125 expression in avian ovarian tumors. METHODS: Immunohistochemistry was employed to evaluate CA125 expression in avian ovarian tumor tissue. A high temperature antigen retrieval step was an essential part of the CA125 staining procedure. In vitro growth curves were constructed for avian ovarian cancer cells. Western blotting was used to estimate the size of the CA125 reactive protein and to confirm CA125 expression. RESULTS: The growth of avian tumors in culture fits a sigmoidal curve for cell growth and suggests a cell cycle time of 28 h. The tumors taken from the chicken stained positive for CA125. Approximately 90% of cells isolated from avian ovarian tumors also stained positive for CA125. Western blots show a band of approximately 25 kDa when immunodetected with CA125. CONCLUSIONS: Similar to human ovarian tumors, chicken ovarian tumors express CA125. Cultured chicken ovarian cancer cells express CA125 and CA125 expression does not appear to change with time in culture.     

血清人附睾分泌蛋白4和CA125水平检测在卵巢恶性肿瘤中的诊断价值

目的 探讨血清人附睾分泌蛋白4(HE4)和CA125水平检测在卵巢恶性肿瘤诊断中的价值.方法 用酶联免疫吸附试验方法 对卵巢恶性肿瘤组(30例)、盆腔良性疾病组(110例,其中卵巢良性肿瘤45例、子宫内膜异位症和子宫腺肌病57例和盆腔炎8例)和正常组(137例)妇女血清中HFA和CA125水平进行双盲检测,结果 以中位数表示,分析两指标单独或联合检测诊断卵巢恶性肿瘤的价值.血清HF4和CA125正常值分别为0～150 pmoVL和0～35 kU/L,单独或联合检测时,其中任一指标高于正常值即定为阳性.结果 (1)卵巢恶性肿瘤组血清HE4和CA125水平分别为244 pmol/L 和601 kU/L,分别与盆腔良性疾病组(分别为32 pmoVL和22 kU/L)和正常组(分别为32 pmol/L和11 kU/L)比较,差异均有统计学意义(P<0.05).卵巢恶性肿瘤组血清HE4单项检测的阳性率为63.3%,明显低于血清CA125项榆测的阳性率(86.7%,P=0.036).(2)单项检测时,以盆腔良性疾病组作参照人群时,HE4和CA125单项检测的受试者工作特征曲线下面积(ROC-AUC)分别为0.900和0.840,其特异度为100%时的敏感度分别为70%和7%,两者比较,差异有统计学意义(P=0.000);以正常组作参照人群时,HE4和CAl25单项检测的ROC-AUC分别0.904和0.914,其特异度为100%时的敏感度分别为67%和87%,两者比较,差异有统计学意义(P=0.031).(3)联合检测时,以盆腔良性疾病组作参照人群时,HE4+CA,笛联合检测和CA125单项检测的ROC-AUC分别为0.894和0.840,其特异度为100%时的敏感度分别为50%和7%,两者比较,差异有统计学意义(P=0.000).以正常组作参照人群时,HE4+CA125联合榆测和HE4单项检测的ROC-AUC分别为0.914和0.904,其特异度为100%时的敏感度分别为87%和67%,两者比较,差异有统计学意义(P=0.031).以盆腔良性疾病组作参照人群时,HE4+CA125联合检测在特异度为100%时的敏感度(50%)虽然低于HE4单项检测(70%),但两者比较,差异无统计学意义(P=0.070).(4)以ROC曲线最左上方的点86 pmol/L、正常组95%参考值50 pmoVL和正常值的上限150 pmol/L为界值点,比较HE4单项检测对卵巢恶性肿瘤的诊断能力,结果 显示,界值点为50 pmol/L时的特异度和阳性预测值分别为95%和63%,明显低于界值点为86(分别为100%和95%)和150 pmoVL(均为100%)时的特异度和阴性预测值(P<0.01).结论 HE4单项检测诊断卵巢恶性肿瘤的特异度优于CA125单项检测,两者联合检测可以提高诊断能力.以150 pmol/L为界值点,对卵巢恶性肿瘤的诊断正确率更高,而以86 pmol/L为界值点有利于卵巢恶性肿瘤的筛查、降低漏诊率.     

CA125阴性卵巢癌血清标志物差异蛋白质组学的研究

目的:通过二维差异凝胶电泳(2-DEDIGE)和基质辅助激光解吸离子化-飞行时间(MALDI-TOF/TOF)串联质谱差异蛋白质组学方法寻找CA125阴性卵巢上皮癌血清标志物,以提高卵巢上皮癌诊断的灵敏度和特异度。方法:收集103例卵巢上皮癌,60例正常对照,63例卵巢良性肿瘤、63例盆腔良性病变的血清。按年龄匹配,选取6例CA125阴性卵巢癌和6例正常对照组的血清等容积混合。祛除血清高丰度白蛋白和IgG后进行2-DEDIGE。实验重复3次。通过DeCyder软件分析得出有显著差异的蛋白质点,MALDI-TOF/TOF鉴定差异蛋白质。分别用WesternBlot和ELISA方法验证获选的血清标志物。结果:(1)经2-DEDIGE实验得出有显著差异的蛋白质点41个,MALDI-TOF/TOF成功鉴定了其中的28个蛋白质点。上调最显著的蛋白质点为结合珠蛋白(haptoglo-bin,Hp),下调最显著的蛋白质为转铁蛋白(transferrin,Tf);(2)WesternBlot和ELISA验证结果显示,CA125阴性卵巢上皮癌血清Hp和Tf与正常对照有显著差异(P<0.001);(3)CA125+Hp+Tf联合检测(两者或两者以上阳性判断为阳性)诊断卵巢上皮癌的灵敏度和特异度高于CA125、Hp和Tf单独检测。结论:Hp和Tf是卵巢上皮癌血清中差异表达的蛋白质,可作为卵巢上皮癌的血清标志物。CA125+Hp+Tf联合检测有助于提高卵巢上皮癌诊断的灵敏度和特异度,有助于提高CA125阴性卵巢上皮癌的检出率。     

Value of CA 125 as a marker of ovarian cancer.

Elevated CA 125 level was noted in 0.2-5.9% healthy women, 2.2-27.8% patients with benign ovarian cysts, and approximately 80% patients with nonmucinous ovarian cancer. In the early stages of cancer, CA 125 level was lower than in the disseminated process (with tendency to higher levels in cases of accompanying exudates to body cavities). The level was found to correlate with the mass of tumor, extent of surgery and response to chemotherapy. Maintenance or increase in CA 125 level after three months of chemotherapy was found to indicate ineffectiveness of the treatment, suggesting a more aggressive therapeutic strategy. The estimation of CA 125 half life after the first two courses of chemotherapy was noted to be a good prognostic factor (9.2 to 10.73 days in patients with total remission, and 22.6 to 44.87 days in patients with progression). The monitoring of ovarian cancer courses using CA 125 level estimations in the serum facilitated decisions at to the timing of the second-look operation; elevated level of the marker was found to indicate that the latter was superfluous. Elevated CA 125 level proceeded clinical diagnosis of relapse by 3 to 6 months, but only in the patients who at earlier stages of the treatment also showed abnormal levels of the marker. The monitoring of patients with complete remission who showed normal CA 125 level throughout the treatment was found useless.