Serum CA 125 levels in epithelial ovarian cancer: relation with findings at second-look operations and their role in the detection of tumour recurrence

Pre-operative serum CA 125 levels were elevated (greater than 35 U/ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second-look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (less than 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second-look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1-17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of less than 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.     

Tumour-associated antigen CA 125 in patients with ovarian cancer

The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6-30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.     

Tumour-associated antigen CA 125 in patients with ovarian cancer

Summary. The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6–30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.     

Serum CA 125 levels in epithelial ovarian cancer: relation with findings at second-look operations and their role in the detection of tumour recurrence

Summary. Pre-operative serum CA 125 levels were elevated (>35U/ ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second-look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (< 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second-look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1–17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of < 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.     

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.     

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.     

The clinical significance of pre-operative serum CA 125 in ovarian cancer

In a prospective study of 52 patients with ovarian malignancy followed up for 3-18 months the clinical significance of pre-operative serum CA 125 as a tumour marker was assessed. In 41 patients with epithelial ovarian cancer, the level of CA 125 correlated well with tumour load as indicated by FIGO stage. All epithelial histological types, including mucinous, released CA 125 although serous and undifferentiated tumours produced quantitatively more antigen. There was, however, no correlation between CA 125 concentration and histopathological grade, nor did CA 125 level appear to be of any prognostic value in epithelial ovarian cancer. Elevated CA 125 levels were also found in patients with sex cord/stromal tumours. Krukenberg tumours, an ovarian sarcoma and a serous carcinoma of low malignant potential.     

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.     

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.     

Initial experiences with CA-15-3 determination in the serum of patients with breast cancer

CA 15-3 levels were determined immunoradiometrically in sera of 63 women with breast cancer (44 with stage I to III cancer, pre-operatively, 5 with local recurrence or lymphnode metastases and 14 patients with distant metastases) and 30 women with benign breast tumours or fibrocystic disease. 32% elevated levels (greater than 25 U/ml) have been found in all carcinomas compared with 7% in 44 patients without any evidence of disease (NED) and 0% in the benign lesions. In locally limited breast carcinomas, the very low pre-operative sensitivity of 16% prevents early tumour detection, whereas in patients with distant metastases a sensitivity of 86% (12 out of 14) has been found. In follow-up, continuous rising of CA 15-3 levels reveals metastatic or progressive disease with a great accuracy, decreasing serum values were only found in cases of remission. A positive correlation between the actual clinical situation in follow-up and the changes in these tumour marker levels has been observed in 87%. The CA 15-3 test system seems to be useful assay for patients with breast cancer with respect to earlier detection of distant metastases, especially of osseous type. This tumour marker is not suitable for screening or early diagnosis of small tumour recurrence in the follow-up of breast cancer patients.     

CA125 Serum Levels and Secondary Laparotomy in Epithelial Ovarian Tumours

CA125 serum levels were assayed prior to 57 secondary laparotomies for ovarian epithelial tumours. Tumour was present in all 16 patients with an elevated level greater than 35 U/ml but the absence of tumour was incorrectly predicted in 15 of the 33 (45.5%) patients with CA125 levels less than 35 U/ml. For these patients the CA125 level was elevated in 14 of 20 (70%) with tumour greater than 1.5 cm, 1 of 7 (14.3%) with macroscopic tumour less than or equal to 1.5 cm and 1 of 4 (25%) with microscopic tumour. Tumour was resectable to less than or equal to 0.5 cm in 7 of 12 (58.3%) patients with CA125 less than 35 U/ml, 2 of 4 (50%) with CA125 in the range 35-100 U/ml and only 1 of 11 (9.1%) with CA125 greater than 100 U/ml (p less than .05). The CA125 level was elevated in 1 of 13 (7.7%) patients with less than 15 cm3 of tumour compared with 16 of 18 (88.9%) patients with 15 cm3 of tumour or more (p less than .0001). The correlation between the CA125 serum level and the tumour volume was almost statistically significant (r = +0.31, p = .053). The level of CA125 was normal in all 8 patients with mucinous tumours--4 of whom were found to have tumour at secondary surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical usefulness of sialyl SSEA-1 antigen as tumor marker for ovarian cancer as compared with CA125, CA19-9, TPA, IAP, CEA and ferritin

In order to determine the clinical significance of sialyl SSEA-1 antigen, we compared its usefulness as a tumor marker for ovarian cancer with simultaneously measured CA125, CA19-9, TPA, IAP, CEA and ferritin. The sialyl SSEA-1 antigen in serum was measured by radioimmunoassay with an "FH-6" Otsuka Kit. The immunohistochemical localization of sialyl SSEA-1 antigen in ovarian carcinoma tissues was determined by an immunoperoxidase method using FH-6 monoclonal antibody. Among fifty-one patients with ovarian cancer, the incidence of elevated serum levels was 54.9% with sialyl SSEA-1 antigen, 90.2% with CA125, 48.8% with CA19-9, 78.0% with TPA, 73.1% with IAP, 17.1% with CEA and 63.4% with ferritin. On the other hand, among the patients with uterine malignancies and gynecologic benign tumors, the incidence of elevated sialyl SSEA-1 antigen levels in serum was lower than that of other tumour markers. In the patients with ovarian cancer, the serum levels of sialyl SSEA-1 antigen increased in accordance with the advance of the clinical stage and were also correlated with the effect of therapy. In the examination of immunohistochemical localization of sialyl SSEA-1 antigen, a positive reaction occurred in 10 out of 30 ovarian carcinoma specimens. Intense staining appeared in the secretory materials, in the luminal surface of the glands, and in the cytoplasm of cells. Thus, sialyl SSEA-1 antigen appears to be a useful tumor marker for the diagnosis of ovarian cancer, especially when measured simultaneously with CA125, CA19-9, TPA, ferritin and IAP.     

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)     

Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen

CA 125 and CA 19-9 are antigenic determinants associated with human epithelial ovarian carcinomas. Murine monoclonal antibodies have been raised against these determinants, and immunoradiometric assays have been developed to monitor antigen levels in the serum of cancer patients. This study was undertaken to determine whether concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen would provide a more precise correlation with tumor progression or regression than could be obtained with any single assay. Among 105 patients with surgically demonstrable epithelial ovarian carcinoma, serum CA 125 levels were elevated (greater than 35 U/ml) in 83%, CA 19-9, levels (greater than 37 U/ml) in 17%, and carcinoembryonic antigen levels (greater than or equal to 2.5 ng/ml) in 37%. Within individual samples, no correlation was found among values for the three markers, but patients with elevated CA 19-9 levels also had increased levels of CA 125. At least one of the three markers was elevated in 90% of the subjects. When 41 patients were monitored serially over 2 to 60 months, alterations in CA 125 levels correlated with disease progression or regression in 94% of instances, whereas alterations in CA 19-9 levels correlated in 33% and alterations in carcinoembryonic antigen levels in 25% of instances. Concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen did not prove superior to measurement of CA 125 alone in the monitoring of patients with epithelial ovarian carcinoma.     

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。     

An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma

Preoperative serum CA 125 levels were determined for 36 patients with Stage I and II ovarian carcinoma. Levels ranged from 9 to 1962 U/ml with a mean of 216 U/ml. In Stage I patients, CA 125 levels averaged 133 U/ml and in Stage II patients 382 U/ml. Nine of 24 Stage I (38%) and 9 of 12 Stage II patients (75%) had CA 125 levels in excess of 65 U/ml in a population somewhat overrepresented in mucinous tumors. Patients with non-mucinous neoplasms had CA 125 elevations more often--in 75% of the cases--than those with mucinous tumors. A larger study will be required to more precisely estimate the fraction of early stage patients with elevated preoperative serum CA 125 levels; however, this investigation demonstrates an assay sensitivity minimally adequate to initiate a pilot evaluation of serum CA 125 levels in a population at risk for ovarian carcinoma.     

A comparison of the usefulness of serum measurements of CA 125, CA 50 and TATI in patients with malignant and benign gynecological pathology

CA 125, CA 50 and Tumor Associated Trypsin Inhibitor (TATI) levels were assayed in blood samples drawn at diagnosis from 149 patients with malignant or benign gynecological pathology. CA 125 serum levels greater than 35 U/ml and 65 U/ml were respectively found in 34/38 (89.5%) and in 33/38 (86.8%) patients with ovarian carcinoma, in 17/61 (27.9%) and in 6/61 (9.8%) with benign ovarian pathology, in 6/30 (20.0%) and in 1/30 (3.3%) with cervical carcinoma, in 6/20 (30.0%) and in 6/20 (30.0%) with endometrial carcinoma. TATI serum levels greater than 22 ng/ml were observed in 17/38 (44.7%) patients with ovarian carcinoma, in 3/61 (4.9%) with benign ovarian pathology, in 1/30 (3.3%) with cervical carcinoma and in 3/20 (15.0%) with endometrial carcinoma. CA 50 serum levels greater than 20 U/ml were found in 11/38 (28.9%) patients with ovarian carcinoma, in 19/61 (31.1%) with benign ovarian pathology, in 7/30 (23.3%) with cervical carcinoma and in 6/20 (30%) with endometrial carcinoma. This study confirmed that CA 125 is the most reliable marker for ovarian carcinoma; however TATI could have a role in the diagnostic evaluation of adnexal masses, because of its very good specificity, CA 125 and CA 50, but not TATI, could be of some benefit in the management of endometrial and cervical carcinoma.     

Increased circulating hepatocyte growth factor (HGF): a marker of epithelial ovarian cancer and an indicator of poor prognosis

Objective

Hepatocyte growth factor (HGF) has been described to be increased in different cancers. In the present study we wanted to investigate whether HGF in serum can distinguish between benign and malignant ovarian tumors, and whether serum HGF levels can predict the outcome in patients with ovarian carcinomas.

Methods

We included 123 consecutive patients appointed for laparotomy due to a pelvic mass. Preoperative levels of serum cancer antigen 125 (CA 125), HGF and HGF activator (HGFA) were quantified with immunological methods. We performed immunohistochemical analyses of HGFα, HGFβ and the receptor c-Met. Five-year survival of patients with advanced disease (stage III and stage IV) was analyzed with the Kaplan-Meier method.

Results

Sixty patients had ovarian carcinomas, 23 borderline tumors, and 40 benign ovarian tumors. Patients with ovarian carcinomas had significantly higher preoperative HGF and CA 125 serum levels than patients with benign ovarian tumors, and borderline tumors. Patients with borderline tumors had significantly higher CA 125 values than benign cases. A combination of CA 125 and HGF increased the specificity in predicting carcinoma. We observed abundant HGFα, HGFβ and c-Met expressions in all ovarian tumors. Patients with advanced disease and preoperative serum HGF values ≥ 2 SD above reference value had a shorter disease-free survival than patients with advanced disease and serum HGF < 2 SD above reference value.

Conclusions

HGF in serum is an indicator of ovarian carcinoma in women with a pelvic mass, and of a poor prognosis in advanced ovarian cancer.     

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。     

Clinical implications of a rising serum CA-125 within the normal range in patients with epithelial ovarian cancer: a preliminary investigation

OBJECTIVE: The goal of this study was to determine the clinical implications of a progressively rising serum CA-125 level in the normal (< 35 U/ml) range in ovarian cancer patients with complete response to therapy. METHODS: A multi-institutional investigation was undertaken to identify patients with CA-125-producing epithelial ovarian cancers who experienced progressively rising antigen levels in the normal (<35 U/ml) range after completion of therapy. All patients had (1) histologic documentation of epithelial ovarian cancer and (2) complete clinical remission (CR) as defined by negative imaging studies, normal clinical examination, and a normal (<35 U/ml) serum CA-125 value. All patients had serum CA-125 determinations at 1- to 3-month intervals after treatment. A rising serum CA-125 level was defined as a progressive increase in at least three CA-125 values above the coefficient of variation (CV) for the assay. No patient had a known episode of pelvic or gastrointestinal inflammatory disease during the period when the progressive rise in serum CA-125 took place. RESULTS: Eleven patients with rising serum CA-125 levels in the normal range were identified. Original stage of disease was as follows: stage IIA, 1; stage IIIC, 10. Cell type was as follows: endometrioid adenocarcinoma, 4; serous adenocarcinoma, 6; clear cell carcinoma, 1. Of the 11 patients identified, all developed recurrent ovarian cancer. Tumor recurrence was documented either by new lesions appearing on imaging studies (6/11) or by histologic confirmation (5/11). The mean time from CR to recurrence was 21 months (median = 22, range = 12-33). The mean time from the third early rising serum CA 125 value to clinical or radiographic confirmation of recurrence was 189 days (range = 84-518). All recurrences were intraabdominal with the exception of one axillary recurrence. CONCLUSION: In patients with a history of ovarian cancer, three progressively rising serum CA-125 values in the normal range (< 35 U/ml) at 1- to 3-month intervals are associated with a high likelihood of tumor recurrence. Patients with such a pattern should undergo immediate investigation to rule out and/or identify recurrent cancer.