Analysis of CA 125 assay system and its diagnostic significance in gynecologic tumors

CA125 antigen levels were measured in patients with ovarian cancer (54 cases) by the RIA method using a monoclonal antibody OC125 and were examined as a marker for ovarian cancer. The upper normal limit of CA125 of 35 U/ml was derived from the mean value (15.7 U/ml)+2SD (9.3 U/ml) of CA125 in healthy controls. The mean value for CA125 in patients with ovarian cancer (1160 +/- 1850 U/ml) was statistically (p less than 0.001) higher than those of healthy controls, benign ovarian tumors (28 +/- 20 U/ml) and cervical cancers (226 +/- 526 U/ml). Elevated CA125 levels were also found in the early pregnant stage and endometriosis, but these cases showed not so high CA125 values as those of ovarian cancers. In addition, CA125 levels were not clearly affected by the menstrual cycle. Among ovarian malignancies, the elevated CA125 values were specifically demonstrated in serous cystadenocarcinoma (positivity 89%) and markedly low in mucinous cystadenocarcinoma (positivity 16%). No positive correlation of CA125 values with the clinical stage (FIGO) were found in any ovarian cancer patients. The rise and fall of CA125 levels corresponded closely with progression and regression of cancer patients with positive CA125 levels. In conclusion, serum CA125 determinations may be useful in patients with ovarian cancer (except for mucinous type) for diagnosis and for monitoring the results of the treatment.     

Studies on serum CA125 levels in pregnant women

To confirm the change in serum CA 125 levels in cases of pregnancy, we measured serum CA 125 levels in 234 normal pregnant women, 40 postpartum women and 14 abnormal pregnant women (12 of IUFD and 2 of H. mole), using an RIA kit. The mean CA 125 level (+/- S.D.) and positive ratio (greater than 34U/ml) for pregnant women at 4-11 weeks of gestation were 65.0 +/- 77.3 U/ml and 64.6%, respectively, being the highest values in all the groups. On the contrary, those for pregnant women at 12-23 weeks of gestation were 22.3 +/- 10.6 U/ml and 12.7%, respectively, the lowest in all gestational groups. Changes in serum CA 125 levels in normal pregnant women showed a trend toward decrease, as gestation advanced. But the CA 125 levels for women at postpartum showed a slight trend toward increase. The mean CA 125 level (+/- S.D.) for 12 patients with IUFD was 392.5 +/- 275.8 U/ml and that for 2 patients with H. mole was 65.0 +/- 15.0 U/ml. Serum CA 125 levels for patients with IUFD were higher than that in cases of normal pregnancy. When utilizing CA 125 as a marker for ovarian cancer, the influence of pregnancy must be considered. And it indicates that CA 125 can be used as an aid to the diagnosis of IUFD in serous cases.     

The Effect of Renal Function on Serum Levels of CA 125

Objective: Serum assays for CA 125 are used to monitor disease status in patients undergoing treatment for epithelial ovarian cancer. While a number of benign gynecologic as well as benign and malignant nongynecologic conditions are associated with CA 125 elevations, the established "normal" range describes a healthy population of women. The metabolism and clearance of CA 125 is not well understood. Because mild degrees of renal impairment frequently occur in ovarian cancer patients, we investigated the effect of impaired renal function on basal CA 125 in a population of female dialysis patients. Methods: Twenty-five women on hemodialysis were selected at random. Patients ranged in age from 29 to 87 years. Renal disease was secondary in most cases to diabetes mellitus or hypertension. The creatinine clearance was less than 10 cc/min for all patients. The duration of dialysis ranged from 3 months to 14 years. Serum levels of CA 125 were measured using monoclonal antibodies in an immunoradiometric assay. Results: The mean of duplicate determinations for 23 of 25 (92%) patients fell within the normal range for otherwise healthy women (<35 U/ml). There was no apparent correlation between CA 125 level and age, menopausal status, BUN, serum creatinine, adequacy of dialysis, or primary underlying diagnosis. Of the 2 patients (8%) with CA 125 levels above the normal range, 1 was premenopausal and the other was postmenopausal; their CA 125 elevations were marginal (49.81 and 50.51). Conclusions: The results of this study demonstrate that even marked renal insufficiency is not itself associated with significant elevations of CA 125 above the normal range selected for otherwise healthy women. The development of renal insufficiency during treatment for ovarian cancer should not alter the interpretation of serum levels of CA 125.     

Preoperative evaluation of CA 125 and CA 19-9 serum levels in patients with ovarian masses

Serum CA 125 and CA 19-9 were presurgically measured in 40 patients with ovarian carcinoma and in 108 with benign ovarian pathologies. The sensitivity for ovarian carcinoma of CA 125 (cut-off value = 65 U/ml) and CA 19-9 (cut-off value = 40 U/ml) were 67.5% and 37.5% respectively. In particular serum CA 125 was elevated in 71.9% of non-mucinous and in 50% of mucinous carcinomas, while serum CA 19-9 was high in 25% of non-mucinous and in 87.5% of mucinous malignancies. The correlation of CA 19-9 with mucinous histotype was significant. Elevated serum levels of CA 125 and CA 19-9 were observed respectively in 14.7% and in 13.8% of benign adnexal masses. The percentages of elevated serum marker levels were significantly higher in patients with ovarian carcinoma than in women bearing benign ovarian pathology (P less than 0.001 for CA 125; P less than 0.01 for CA 19-9). Serum CA 125 and CA 19-9 alone cannot clarify the nature of an adnexal mass. However, the measurement of serum levels of these markers could give additional information to other diagnostic methods, such as ultrasonography, for discriminating benign from malignant ovarian pathologies.     

Clinical evaluation of specificity of serum CA125 as a tumor marker of ovarian carcinoma

To evaluate whether elevated serum CA125 levels have specificity to ovarian malignancies, CA125 levels were measured in sera of 48 malignancies, 56 benign diseases and 40 healthy women. Furthermore serum CA125 levels were serially followed up in all the patients with positive serum CA125 levels (35 U/ml less than or equal to) to evaluate the correlation between serum CA125 levels and the response to treatment. Results obtained were as follows. A significantly higher positive rate (91%) of serum CA125 levels was observed in patients with ovarian malignancies than that (30%) in patients with other malignancies. Positive serum CA125 levels were also observed in patients with endometriosis, benign ovarian tumor, hydrosalpinx, uterine myoma and peritoneal tuberculosis. Serum CA125 levels in patients with malignancies depend on the volume of the solid part of the tumor irrespective of the tumor type. In patients with positive serum CA125 levels, rising or falling of the serum levels of this antigen correlated well with progression or regression of all kinds of diseases. These results suggested that a high positive rate of this antigen in patients with ovarian malignancies was not merely derived from the tumor specificity of this marker but partly from the fact that tumor sizes of ovarian malignancies were generally larger than those of other malignancies.     

Use of serum secretory leukocyte protease inhibitor levels in patients to improve specificity of ovarian cancer diagnosis

OBJECTIVE: To assess the clinical relevance of serum secretory leukocyte protease inhibitor (SLPI) levels in distinguishing patients with ovarian cancers from those with benign ovarian cysts, we determined concentrations with reference to the FIGO stage and other clinical characteristics. METHODS: Preoperative serum SLPI levels were measured in women with invasive epithelial ovarian cancer (n = 55), benign ovarian cysts (n = 25), or normal controls (n = 38) using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum SLPI concentration was significantly elevated in the ovarian cancer patients (median 67 ng/ml, interquartile range 26-124 ng/ml) as compared to the benign cyst patients (37 and 25-66 ng/ml) or healthy women (32 and 25-43 ng/ml). Using an SLPI cutoff of 50 ng/ml and a CA125 cutoff of 30 units/ml, with both markers elevated the sensitivity was 95%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 89% between the malignant and benign cyst patients. CONCLUSION: Serum SLPI levels could be useful for differentiating benign ovarian cysts from malignancies and to improve the specificity of diagnosis.     

Evaluation of CA125 as a circulating tumor marker for ovarian cancer

CA125 usefulness was evaluated using sera from healthy persons, pregnant women, and patients with ovarian and other tumors. Since serum CA125 levels significantly depended on sex and age in healthy persons, the original cut-off levels were 40 and 25 U/ml in terms of sex and age. Changes in CA125 levels within 40 U/ml were observed during the menstruation cycle. Elevation of CA125 levels was also observed during the first trimester of pregnancy, but these levels fell below 50 U/ml as pregnancy progressed. Immunostaining of the endometrium with OC125 suggested that ovarian function may play an important role in production of CA125 in early pregnancy and menstruating young women. Elevated levels of CA125 were detected in 33/34 (97%) cases with surgically demonstrated ovarian cancer. The clinical usefulness of CA125 for monitoring the course of ovarian cancer was reconfirmed. Practical application of CA125 proved to be useful for the early detection of ovarian cancer and confirmation of the complete disappearance of any tumor.     

CA 125 in the serum and tissue of patients with gynecological disease

Summary Serum levels of CA 125 were determined in 239 patients suffering from gynecological malignancies. The upper limit for normal was 35 U/ml. Raised levels were found in 82% of patients with primary ovarian carcinoma, and in 29% of those with benign ovarian tumors. The values from patients with ovarian carcinomas in partial or complete remission were compared with those from patients with progressive disease. The former group had elevated levels in 19% compared to 89% in the latter group. Fifty-four percent of the values in progressive cervical carcinoma and 41% of the levels in progressive endometrial carcinoma were greater than 35 U/ml. High CA 125 levels were found in the cytosol of placenta, ovarian carcinoma, cervical carcinoma, and in ascitic fluid; correlation with serum levels was satisfactory. Even though CA 125 is of limited specificity for ovarian cancer, serum levels are important for follow up care and for the early detection of recurrences.     

Serum soluble Fas levels in ovarian cancer

OBJECTIVE: To determine the value of serum soluble Fas levels as a prognostic marker for survival of women with ovarian cancer and as a discriminator between benign and malignant adnexal masses. METHODS: Serum soluble Fas levels were measured with an enzyme-linked immunosorbent assay in 52 women with ovarian cancer, 30 women with benign ovarian cysts, and 35 healthy women. RESULTS: Median serum soluble Fas levels in women with ovarian cancer, women with benign ovarian cysts, and healthy women were 3.7 (range 1.6-14.5), 2.3 (range 1.3-4.1), and 1.5 ng/mL (range 0.1-5.6), respectively (P <. 001). A univariate logistic regression model showed a significant influence of serum soluble Fas and CA 125 levels on the odds of presenting with ovarian cancer versus benign cysts (P <.001 and P =. 001, respectively). In a multivariable logistic regression model for soluble Fas and CA 125, both markers showed a statistically significant influence on the odds of presenting with ovarian cancer versus benign cysts (P =.01 and P =.01, respectively). Increased pretreatment serum soluble Fas levels were associated with shortened disease-free and overall survival (P =.002 and P =.001, respectively). A multivariable Cox regression model identified serum soluble Fas levels as a significant prognostic factor for disease-free and overall survival, independent of tumor stage (P =. 04 and P =.03, respectively). CONCLUSION: Soluble Fas levels might be useful as a discriminator between benign ovarian cysts and ovarian cancer, adding to the information obtained with the use of the established tumor marker CA 125. Pretreatment serum soluble Fas levels also might be an independent prognostic factor for disease-free and overall survival.     

Clinical significance of new tumor marker CA 125 in gynecological cancer--particularly usefulness in diagnosis of ovarian cancer

A concentration in sera of a new antigen CA125 related to cancer of the ovary was measured by radioimmunoassay which used a monoclonal antibody, and its usefulness as a tumor marker in the diagnosis of cancer of the ovary was investigated. The mean values for CA125 in sera of healthy controls (80 females) were 14.2 +/- 12.2 U/ml. Mean values for CA125 in sera of various patients were 29.0 +/- 39.6 for myoma uteri (30 cases), 26.7 +/- 30.1 for benign ovarian tumors (10 cases), 64.4 +/- 146.2 for cervical carcinoma (14 cases), and 31.5 +/- 19.8 for endometrial carcinoma (6 cases), whereas the mean values for ovarian cancers (23 cases) were as high as 311.3 +/- 250.4. On the other hand, positive rates for CA125, when the cut-off value was set to 65 U/ml, were 1.3% for healthy controls (1 out of 80 cases), 10.0% for myoma uteri (3 out of 30 cases), 10.0% for benign ovarian tumors (1 out of 10 cases), 14.3% for cervical carcinoma (2 out of 14 cases), and 16.7% for endometrial carcinoma (1 out of 6 cases), whereas the positive rate for ovarian cancers was 78.3% (18 out of 23 cases). Especially for serous cystadenocarcinoma, the positive rate was 100% (10 out of 10 cases). From the above, the measurement of CA125 in sera was considered to be significant in the diagnosis of ovarian cancer.     

Use of CA 125 monoclonal antibody to monitor patients with ovarian cancer

The monoclonal antibody (mAb) OC 125 reacts with an antigen on human ovarian carcinoma (OVCA) cells that is also shed into the body fluids and can be detected in patients' sera and/or ascites with a radioimmunometric assay. For the present study, serum CA 125 levels of patients (n = 36) with different stages of OVCA were investigated. Serum levels seem to correlate with tumor burden. In stages I and II (n = 12), 33% of patients were CA 125 positive, whereas 70% of stage III and IV patients (n = 24) were CA 125 positive. Mean serum levels were in 93 U/ml (stages I, II) and 279 U/ml (stages III, IV). CA 125 levels in ascites and in pleural effusions were manyfold higher than serum levels of the same patients (P less than 0.0001). Immunohistochemical investigations of CA 125 in different ovarian tumors (n = 91) revealed that 85% of malignant and 75% of borderline serous cystadenocarcinomas had detectable CA 125 surface expression. Furthermore, 71% of benign tumors showed the CA 125 epitope, whereas mucinous tumors were negative for this marker. One of six ovarian cancer cell lines was CA 125 positive, whereas in 6 of 11 patients, ascites-derived ovarian cancer cells (fresh and gradient isolated) were positive for this marker. The proportion of positive cells ranged from 10 to 90% in these samples. Intraperitoneal recombinant interferon-gamma (rIFN-gamma) therapy resulted in an increase in the number of cells reacting with CA 125. The results of monitoring in patients receiving different therapeutic regimens and/or agents demonstrate the usefulness of this marker.     

CA 125 in gynecologic practice

Serum CA 125 levels were determined in 64 women with benign ovarian lesions, 92 women with uterine fundal lesions, and six patients who had negative second-look laparotomy for epithelial ovarian carcinoma. Of those with benign lesions, 13 of 31 patients with endometriosis had levels greater than 35 U/ml. Six of 34 patients with endometrial carcinoma had elevated levels before the primary operation, and six of 15 patients with recurrent endometrial carcinoma had elevated levels. The six ovarian cancer patients had had negative findings at second look 7 to 40 months before recurrence. Where close serial levels were available, the level became elevated 2 to 5 months before clinically apparent recurrent disease was noted.     

Evaluation of CA 125 levels in differentiating malignant from benign tumors in patients with pelvic masses

Serum CA 125 levels were assayed from 44 normal healthy women, 153 patients with benign pelvic masses, and 58 patients with malignant pelvic masses. CA 125 levels were less than 35 U/mL in 42 of the 44 normal women and were greater than 35 but less than 65 U/mL in the other two women. Among 153 patients with benign pelvic masses, CA 125 levels greater than 35, 65, or 194 U/mL were detected in 61 (39.9%), 31 (20.3%), and eight (5.2%) patients, respectively. Of 58 patients with malignant pelvic masses, CA 125 results were greater than 35, 65, or 194 U/mL in 48 (82.8%), 45 (77.6%), and 38 (65.5%), respectively. Among the latter group, the positivity rates of 30 patients with epithelial ovarian cancers were 100, 93, and 80%, respectively. This study suggests that defining positive serum CA 125 levels as those greater than 35 U/mL is of limited clinical value because there is a 39.9% false-positive rate in patients with benign disease. However, serum CA 125 values greater than 65 U/mL may be considered positive in clinically normal women. Serum CA 125 greater than 194 U/mL, representing the units at the 95th percentile for 153 patients with benign pelvic masses, is defined as a new positivity criterion, and could be used to differentiate malignant tumors from benign pelvic masses.     

Evaluation of HE4 as an extrabiomarker to CA125 to improve detection of ovarian carcinoma: is it time for a step forward?

Purpose

To evaluate human epididymis protein 4 (HE4) as an extrabiomarker to cancer antigen 125 (CA125) to improve the detection of ovarian carcinoma.

Methods

Sixty patients with ovarian carcinoma, 50 patients with benign ovarian tumors and 30 healthy women were included in the present study. Serum concentration of HE4 was assayed using ELISA technique, while CA125 was assayed using chemiluminescent enzyme immunoassay.

Results

The median CA125 and HE4 serum values were significantly higher among ovarian cancer patients when compared with healthy control However, the median serum levels of CA125 but not HE4 were significantly higher among patients with benign ovarian tumors as compared to healthy women. Based on the receiver operator characteristics curve analysis, HE4 had higher sensitivities than CA125 for the detection of ovarian cancer at 90, 95 and 98 % specificities and the combination of both markers yielded a higher sensitivity than either alone. However, CA125 but not HE4 had higher sensitivities for the detection of benign ovarian tumors at the same specificities. In addition, a positive correlation was observed between HE4 and CA125 among patients with ovarian carcinoma.

Conclusion

HE4 is a valuable marker for ovarian cancer diagnosis and when combined with CA125, they had a higher sensitivity at a set specificity, thus providing a more accurate predictor of ovarian cancer than either alone.     

Comparison between serum CA 125 and CA 19-9 assays and tissular OC 125 and 1116NS 19-9 reactivity in malignant and benign ovarian tumors.

This preliminary study included 25 patients with primary epithelial ovarian cancer (EOC) (18 serous, 3 serous-mucinous, 1 endometrioid, 2 undifferentiated carcinomas and 1 malignant Brenner carcinoma); 2 patients with borderline ovarian tumors and 20 patients with benign ovarian tumors (9 benign cystic teratomas, 6 serous cystoadenomas and 5 mucinous cystoadenomas). Blood samples for the measurement of CA 125 and CA 19-9 were drawn from all patients before surgery. Serum CA 125 (Reference Value-RV = 65 U/ml) and CA 19-9 (RV = 40 U/ml) were measured with IRMAs using the monoclonal antibodies (MoAbs) OC 125 and 1116NS 19-9. The same antigens were detected on paraffin-embedded tissue sections by immunocytochemistry with the avidin-biotin complex method employing the same MoAbs used for serum IRMAs. Among the 25 patients with EOC serum CA 125 levels were elevated in 20: tissular OC 125 reactivity was observed in 15 (75%) of them. Of the 5 EOC patients with normal CA 125 levels, 4 showed OC 125 reactivity. Only 2 of the 25 EOC patients had elevated serum CA 19-9 levels: one of them had tissular 1116 NS 19-9 reactivity. Among the 23 patients with normal serum CA 19-9 levels only 5 had immunocytochemical reactivity for this antigen. The 2 patients with borderline ovarian tumors had negative serum CA 125 and CA 19-9 assay: tissular OC 125 reactivity was observed in both patients, while 1116 NS 19-9 reactivity was detected in only one.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.     

4种肿瘤标志物对上皮性卵巢癌定性诊断价值的初步研究

目的：探讨多胺（ＰＡ）、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９在定性诊断上皮性卵巢癌中的价值。方法：应用ＨＰ％Ｍ高效液相色谱仪和ＨＰ１０４０Ａ荧光检测器或酶联免疫吸附法测定上皮性卵巢癌４０例和卵巢良性肿瘤１８例血清中ＰＡ、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９水平。结果：４种标志物中，ＰＡ诊断卵巢癌的敏感性、阳性预测率、阴性预测率和预测准确率最高，其次是ＣＡ１２５。结论：ＰＡ对人类恶性肿瘤缺乏特异性，但可作为鉴别卵巢良、恶性病变的有价值标志物。联合测定ＰＡ和ＣＡ１２５时，其敏感率为９４．９％。因此，联合测定ＰＡ和ＣＡ１２５可作为筛查卵巢良、恶性肿瘤的方法。     

组织多肽抗原在卵巢癌诊断及监测中的应用

目的评价组织多肽抗原（ＴＰＡ）在卵巢癌诊断和监测中的临床价值。方法应用放射免疫方法测定了２４例正常妇女、２７例妇科良性疾患及６０例卵巢癌患者的血清ＴＰＡ及ＣＡ１２５值并进行比较分析。结果ＴＰＡ在卵巢上皮性癌患者中的异常检出率为８２％,ＣＡ１２５为７０％,二者总的异常检出率为９２％。在绝大多数正常妇女和卵巢良性肿瘤患者中,ＣＡ１２５和ＴＰＡ在正常范围。作为卵巢癌相关标志物,ＴＰＡ与ＣＡ１２５具有相似敏感性。１９例动态观察结果显示,ＴＰＡ和ＣＡ１２５二者与病情转归是一致的。结论ＴＰＡ和ＣＡ１２５联合应用对卵巢癌的鉴别诊断及提高总的异常检出率具有价值。     

Differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis by a combination assay of serum sialyl SSEA-1 antigen and CA125 levels

We used a combination assay of serum sialyl SSEA-1 antigen (SLX) and CA125 levels, and evaluated the clinical usefulness of this technique for a differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis. In 82 patients with ovarian tumors, the sera of 20 (64.5%) of 31 with ovarian cancer and 15 (48.4%) of the 31 with endometriosis (endometrial cyst) were positive for both SLX and CA125, but serum SLX level was 5 U/ml or less in these 14 SLX- and CA125-positive patients with endometriosis. The sera of 16 (80.0%) patients with benign ovarian tumor were negative for both tumor markers. The sera of 3 (9.7%) of 31 with ovarian cancer and the sera of 2 (6.5%) of 31 with endometriosis were negative for both markers. The diagnostic accuracy (true positive rate X true negative rate) of the combination assay for ovarian cancer was 49.0% when the cutoff value of the serum SLX was 38 U/ml but improved to 78.5% when the value was set at 50 U/ml. When the cutoff value of serum SLX was set at 50 U/ml and that of serum CA125 at 35 U/ml, 27 of 37 patients who were positive only for CA125 had endometriosis. From the above observations, a combination assay of serum SLX and CA125 is a promising method for the differential diagnosis of malignant and benign ovarian tumors. Our results also suggest that to improve the diagnostic accuracy, the cutoff value of the serum SLX level should be 50 U/ml for ovarian tumors alone.     

The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis.

The serum levels of CA 125 (cutoff limit, 65 U/ml), CA19.9 (cutoff, 40 U/ml), CA 15.3 (cutoff, 32 U/ml), CA72.4 (cutoff, 3.8 U/ml), and TATI (cutoff, 22 ng/ml) were preoperatively measured in 90 patients with epithelial ovarian cancer and in 254 patients with benign ovarian pathology. CA125 had a sensitivity of 75.6%, a specificity of 86.6%, and a diagnostic accuracy of 83.7% for epithelial ovarian cancer; CA19.9 had a sensitivity of 35.6%, a specificity of 81.1%, and a diagnostic accuracy of 69.2%; CA15.3 had a sensitivity of 57.1%, a specificity of 93.9%, and a diagnostic accuracy of 84.6%; CA72.4 had a sensitivity of 70.7%, a specificity of 91.8%, and a diagnostic accuracy of 86.2%; and TATI had a sensitivity of 47.3%, a specificity of 95.3%, and a diagnostic accuracy of 82.9%. CA 125 was the most sensitive marker for nonmucinous tumors, while CA19.9 and CA72.4 were the antigens more frequently expressed by mucinous malignancies. The sensitivities of serum CA 125 (81.1% vs 50.0%; P = 0.01) and TATI (55.2% vs 18.8%; P = 0.02) were higher in patients above 50 years of age than in younger patients while specificities were quite similar in both age groups. The association of serum CA125 and CA19.9 had a significantly higher sensitivity (93.2% vs 81.1%; P = 0.03) and a slightly lowered specificity (78.9% vs 86.0%; P = 0.46) than CA125 assay alone in the differential diagnosis of ovarian masses in patients above 50 years of age.