Experiments with tissue cultures from a human ovarian serous cystadenocarcinoma producing cancer antigen 125 (CA125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA)

Summary The patient was a 57-year-old woman with ovarian serous cystadenocarcinoma in FIGO clinical stage IV. Cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) were immunohistochemically demonstrated in tumor cells, and the variations of serum CA125 and TPA levels reflected the clinical course. The tumor tissue obtained at exploratory laparotomy was minced with scissors, and transplanted subcutaneously into female nude mice for in vivo maintenance. The tumor cells from 5th generation nude mice were dispersed in Eagle's minimal essential medium supplemented with 10% fetal calf serum, and incubated in Falcon tissue culture dishes at 37°C in 5% CO₂ in air for in vitro maintenance. The results were as follows: Histopathologically the tumor transplanted into nude mice showed a cystadenocarcinoma, which closely resembled the original human tumor. Immunohistochemically CA125, TPA and CEA were demonstrated in the tumor transplanted into nude mice as well as in the original human tumor. From the growth curve in nude mice, the doubling time was estimated to be about 3.5 days. Serum TPA levels in nude mice were increased in proportion to the tumor growth after transplantation, but serum levels CA125 and CEA were normal. The concentrations of CA125 and TPA were increased in the conditioned media compared with the control media, although the elevated values were decreased with subsequent passages. CEA concentrations in the conditioned media were unchanged.     

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)     

The role of cancer antigen 125 (CA 125) in the management of ovarian epithelial carcinomas

From June 1, 1984, to May 31, 1985, 98 cases of epithelial ovarian carcinomas were assessed and followed prospectively using a new murine monoclonal antibody OC 125 which detects the antigen CA 125. Serous tumors comprised 43.7% of cases, mucinous tumors 20.4%, endometrioid tumors 16%, and other epithelial tumors 19.4%. Tumors of low malignant potential and benign epithelial cystadenomas were not included. For this study the upper limit of normal for CA 125 was 20 U/ml. Thirty-six were new cases. In this group the initial CA 125 levels greater than 20 U/ml, greater than 35 U/ml, and greater than 65 U/ml were 97.2, 94.4, and 86.1%, respectively. When mucinous types were excluded the specificity rate did not change significantly. There was no significant difference in initial CA 125 levels between early stages I and II and late stages III and IV. No correlation between tumor bulk and the serum level of antigen was observed. The remaining 62 patients were being followed and in this group 50 were considered to be in remission. Six cases in the remission group had elevated CA 125 levels greater than 20 U/ml and 5 of these developed clinical recurrence. The correlation between the clinical status and concordant fluctuations in the serum levels of CA 125 in all histological types was 87.8 and 93.5% when 10 cases of mucinous tumors were excluded. The contingency coefficient was 0.746. Seven SLOs were performed. All had CA 125 levels less than 20 U/ml and the mean was 6.9 U/ml. Only 1 case was positive with microscopic disease. In our experience CA 125 was invaluable in the management and follow-up of patients with ovarian carcinoma especially for the early detection of recurrent disease and for the monitoring of patients on therapy.     

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.     

CA_(125)、CA_(19.9)、CEA在卵巢上皮性交界性肿瘤中的临床价值

目的 :探讨测定血清CA12 5、CA19.9、CEA在诊断卵巢上皮性交界性肿瘤中的临床价值。方法 :回顾分析卵巢交界性肿瘤 5 0例血清CA12 5、CA19.9、CEA水平与临床资料。结果 :浆液性及粘液性肿瘤中CA12 5的阳性率分别为 5 3.85 %和 60 % ,差异无显著性 (P >0 .0 5 ) ,临床分期晚者CA12 5阳性率有增高趋势 ;粘液性肿瘤中CA19.9的阳性率为 4 3.75 % ;CEA阳性率为 12 % ,仅见于粘液性或以粘液性为主的肿瘤中 ;与术前相比 ,术后CA12 5、CA19.9水平及阳性率均显著下降 (P <0 .0 5 )。结论 :CA12 5、CA19.9对卵巢上皮性交界性肿瘤的术前诊断及疗效监测有一定价值 ,CEA则在鉴别组织学类型中有一定价值。     

Relationship between serum levels and immunohistological tissue levels of CA 125 and CEA in epithelial ovarian cancers: its implications for tumor cell type specificity

Tissue localization and serum levels of CA125 and CEA in patients with epithelial ovarian tumors were examined. In patients with serous cystadenocarcinoma, "high CA125 and low CEA" was a characteristic feature in the serum, while in patients with mucinous cystadenocarcinoma, "low CA125 and high CEA" was generally found in the serum. Tissue localization of CA125 was strongly positive in serous cystadenocarcinoma associated with high serum CA125 levels, and negative in serous tumors showing normal serum CA125 levels. In mucinous cystadenocarcinoma, CA125 staining was positive with a minimum intensity. Immunostaining of CEA was strongly positive in mucinous cystadenocarcinoma associated with high serum CEA levels and was negative in mucinous tumors showing normal serum CEA levels. Tissue localization of CEA in serous cystadenocarcinoma was negative. There was a good correlation between serum CA125 and immunohistochemical tissue levels of CA125 in serous cystadenocarcinoma, and the same between serum CEA and immunohistochemical tissue levels of CEA in mucinous cystadenocarcinoma. These results demonstrate that in epithelial ovarian tumors CA125 has a relatively higher tumor cell type specificity for serous cystadenocarcinoma, whereas CEA does for mucinous cystadenocarcinoma.     

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.     

Serum levels of six tumor markers in patients with benign and malignant gynecological disease

Summary We studied the pretreatment serum levels of 6 tumor markers in gynecological patients with and without malignant disease. The tumor markers were carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, Schwangerschaftsprotein 1 (SP₁), Schwangerschaftsprotein 3 (SP₃) and cancer antigen 125 (CA125). The results were as follows: (1) Serum CA125 and TPA levels were raised in 81% and 57% of patients with ovarian serous cystadenocarcinoma: CEA and SP₃, in 52% and 43% respectively of patients with ovarian mucinous cystadenocarcinoma; CA125, TPA and SP₃, in 76%, 48% and 48% respectively of patients with other ovarian malignancies; and TPA and SP₃, in 56% and 40% respectively of patients with endometrial carcinoma. (2) Serum levels of TPA, ferritin and CA125 were more often raised with advancing stages of malignant disease. (3) Serum TPA levels were elevated in 55% of patients with stage I endometrial carcinoma, and serum SP₃ levels were elevated in 35% of patients with a stage I malignant ovarian neoplasm and in 45% of patients with endometrial carcinoma. (4) One of the 6 tumor markers showed a raised level in 84% of patients with gynecologic malignancy as against 56% in those with benign gynecologic diseases.     

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.     

Immunohistochemical study of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) in the human and cynomolgus monkey placenta,umbilical cord and decidua

Summary Tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) were studied immunohistochemically by the avidin-biotin immunoperoxidase technique in human and cynomolgus monkey placentae, membranes, umbilical cords and decidua. In early human placentae, TPA was localized mainly in the cell membranes of villous syncytio- and cyto-trophoblast. The cytoplasm of those trophoblastic cells were weakly stained with TPA. The membrane of basal chorionic trophoblast cells was strongly stained with TPA and the cytoplasm stained weakly. In early cynomolgus placentae, similar immunostaining results were obtained. However, the positive stainings for TPA was more marked in the cytoplasm of villous syncytiotrophoblast and basal chorionic trophoblast, and less marked in the cell membrane of villous cytotrophoblast. In early human and cynomolgus placentae, CA125 was not demonstrated immunohistochemically in the villi and basal chorion. In human and cynomolgus term placentae, the villous syncytiotrophoblast and basal and reflected chorionic trophoblast showed similar immunostaining as the early placentae. In addition, TPA was found in the amniotic epithelium in both sorts of placentae. TPA was not detected immunohistochemically in the umbilical cord and decidual cells. While weakly positive stains for CA125 were observed in decidual cells, CA125 was localized mainly in the membrane and cytoplasm of amniotic epithelium in both human and cynomolgus term placentae. TPA and CA125 are thus oncoplacental antigens and the monkey could serve as a model for their investigation.     

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。     

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 use of CA 125 and its combination assay with other tumor marker in patients with ovarian carcinoma

The serum levels of CA 125 and CA 19-9 were determined by an immunoradiometric assay employing the monoclonal antibody OC 125 and anti-CA 19-9 antibody in 88 patients with ovarian carcinoma. When a cut-off value of CA 125 was set below 35 U/ml in the control group, serum elevated levels of CA 125 were found in 86.7% of the patients with surgically demonstrable ovarian serous cystadenocarcinoma, in 100% (4/4 cases) of clear-cell carcinoma, in 50% (2/4 cases) of endometrioid carcinoma, in 100% (5/5 cases) of undifferentiated carcinoma, and in 80% of the recurrent cases. Using a cut-off value of 37 U/ml, serum elevated levels of CA 19-9 were detected in 68.2% of mucinous cystadenocarcinoma, in 28.9% of serous cystadenocarcinoma, in 75% (3/4 cases) of metastatic ovarian carcinoma, and in 37.5% of the recurrent cases. A statistical analysis of the combination assay using CA 125, CA 19-9, tissue polypeptide antigen (TPA), immunosuppressive acidic protein (IAP), ferritin and CEA was carried out by multivariate method (discriminatory analysis) in 45 patients with ovarian carcinoma and 50 healthy subjects. As a result before treatment, positive rates of a single tumor marker were 79.7% with CA 125, 42.7% with CA-19-9, 73.1% with IAP, 61.7% with TPA, 64.3% with ferritin and 25.4% with CEA, respectively. A combination assay of these markers was useful for detecting identification of ovarian carcinoma, by which it gave a higher accuracy of ovarian cancer detection.     

Carcinoembryonic antigen (CEA) and carbohydrate determinant 19-9 (CA 19-9) localization in 121 primary and metastatic ovarian tumors: an immunohistochemical study with the use of monoclonal antibodies

An immunoperoxidase study, using the Avidin-Biotin-Peroxidase complex method and the monoclonal antibodies, anti-carcinoembryonic antigen (CEA) and anti-carbohydrate determinant 19-9 (CA 19-9), was carried out on 108 common epithelial tumors of the ovary and 13 epithelial tumors metastatic to the ovary. Primary mucinous tumors were positive in 62% of the cases (benign, 15%; borderline, 80%; and carcinomatous, 100%) with anti-CEA. None of the serous tumors were positive with anti-CEA, but 27% (benign, 23%; borderline, 40%; and carcinomatous, 20%) were positive with anti-CA 19-9. With anti-CEA, 30% of the endometrioid carcinomas, 50% of the malignant mesodermal mixed tumors, 14% of the clear cell carcinomas, 36% of the Brenner tumors, and 83% of the metastatic carcinomas from the large intestine were positive. With anti-CA 19-9, 76% of the mucinous, 40% of the endometrioid, 25% of the malignant mesodermal mixed tumors, 57% of the clear cell carcinomas, 45% of the Brenner tumors, and all the metastatic carcinomas from the large intestine were positive. All the undifferentiated carcinomas were unreactive with both antibodies. Although neither CEA nor CA 19-9 is a specific marker for any type of ovarian tumor or for malignancy per se, the presence of the former antigen can be useful in differentiating serous from mucinous tumors. Moreover, demonstration of either antigen in a variety of tumors may indicate its potential value as a serum marker in monitoring the course of the patient.     

CA19-9、CA125和CP2在卵巢黏液性肿瘤诊断和监测中的价值

目的探讨血清肿瘤标志物CA19-9、CA125及CP2在卵巢黏液性肿瘤诊断和监测中的价值。方法对北京大学人民医院1999年1月至2007年6月间收治的273例卵巢肿瘤患者的临床资料进行回顾性分析,探讨血清肿瘤标志物CA19-9、CA125及CP2在50例卵巢黏液性肿瘤诊断和监测中的价值,并与223例卵巢非黏液性肿瘤进行比较。结果（1）卵巢黏液性肿瘤中,CA19-9的曲线下面积最大（为0．95）,其次是CA125（为0．90）;而卵巢非黏液肿瘤中,CA125和CP2的曲线下面积最大（均为0．90）。（2）卵巢黏液性肿瘤患者联合检测CA19-9和CA125时,其敏感度（93．8％）较单项检测（CA19-9和CA125分别为75．0％和66．7％）明显提高（P〈0．05）,而特异度（分别为86．1％、86．6％和90．2％）无明显变化（P〉0．05）。卵巢非黏液性肿瘤患者联合检测CA125和CP2时的敏感度（85．0％）,较CP2（70．6％）单项检测明显提高,差异有统计学意义（P〈0．05）;较CA125（80．7％）单项检测虽有提高,但差异无统计学意义（P〉0．05）;3者的特异度（分别为90．2％、88．5％和93．9％）比较,差异无统计学意义（P〉0．05）。（3）82例卵巢恶性肿瘤术前血清肿瘤标志物阳性患者中。可行满意的肿瘤细胞减灭术患者[70％（57／82）]的血清肿瘤标志物于术后2个月内降为正常的百分率高于未能行满意肿瘤细胞减灭术者（分别为75％和28％）,差异有统计学意义（P〈0．05）;且其术后血清肿瘤标志物再次上升的平均时间延长（分别为18．2和16．4个月）,但差异无统计学意义（P〉0．05）;复发率（分别为35％和56％）及死亡率（分别为14％和32％）降低,差异有统计学意义（P〈0．05）。20例术前血清肿瘤标志物阴性患者均可行满意的肿瘤细胞减灭术,其中复发患者仅2例（10％）。（4）卵巢黏液性肿瘤患者术后复发时多为血清CA19-9水平上升,而卵巢非黏液性肿瘤术后复发时主要为血清CA125水平上升,部分患者血清CP2水平也上升。（5）术前血清肿瘤标志物阳性患者较阴性患者生存率明显下降,其中CA125（＋）与CA125（-）、CP2（＋）与CP2（-）患者间生存率比较,差异有统计学意义（P〈0．05）;而CA19-9（＋）与CA19-9（-）患者间生存率比较,差异则无统计学意义（P〉0．05）。结论CA19-9是诊断卵巢黏液性肿瘤的敏感指标,与CA125联合检测可提高对卵巢黏液性肿瘤诊断的敏感度,并对术后监测有重要临床意义。CA125和CP2联合检测则对诊断卵巢非黏液肿瘤更敏感。     

Periodic acid-Schiff stain as a prognostic indicator in serous and mucinous ovarian tumors

The prognostic significance of periodic acid-Schiff (PAS) stain in 112 serous: 43 benign, 25 borderline and 44 malignant cystadenomas: and in 106 mucinous: 60 benign, 32 borderline and 14 malignant cystadenomas of the ovary were investigated. The amount of positively stained mucin was estimated morphometrically. The outcome of most patients with benign or borderline lesion was good. One patient with benign mucinous cystadenoma died, however, of pseudomyxoma peritonei and another patient with borderline mucinous cystadenoma died of peritoneal carcinosis. Other patients were alive and free of the disease after a follow-up of 1-14 years, or had died of causes unrelated to the ovarian disease. Abundant PAS positive mucin predicted a longer survival both in serous and in mucinous malignant tumors. The 5-year survivals for the serous cystadenocarcinomas with and without PAS positive mucin were 21% and 13%, respectively (not statistically significant). For mucinous cystadenocarcinomas with mucin value over and below the median, the 5-year survival rates were 57% and 14%, respectively (P less than 0.10). High PAS positivity in both serous and mucinous cystadenocarcinomas clearly indicated better prognosis, although statistical significance was not achieved. Thus, further studies are needed for final evaluation of the prognostic significance of the PAS stain in these ovarian tumors.     

Tissue expression of CA 125 in benign and malignant lesions of ovary and fallopian tube: A comparison with CA 19-9 and CEA

Sections of formalin-fixed and paraffin-embedded tissue specimens of 11 normal ovaries and tubes, 13 tubo-ovarian abscesses, 3 tubal carcinomas, and 115 ovarian tumors were investigated by immunohistochemistry. CA 125 and CA 19-9 were demonstrated with monoclonal antibodies, CEA with polyclonal antibodies. The tissue expression was visualized by the avidin-biotin method. In the germinal epithelium of all ovaries no tumor marker was confirmed. In 4 out of 11 tubes the epithelium was CA 125 positive, in 2 out of 11 cases CA 19-9 positive. Nine out of 13 tubo-ovarian abscesses were CA 125 and 5 out of 13 were CA 19-9 positive in their epithelium. Elevated serum levels of these markers might be due to expression via the epithelial cell of the inflamed tube. All normal and inflammatory adnexal tissues were CEA negative. In serous tumors and undifferentiated carcinomas, CA 125 was most frequently confirmed (85 and 70%, respectively). All mucinous tumors were CA 125 negative. The most frequently confirmed tumor marker was CA 19-9 (77%). In endometrioid tumors, CEA was most frequent (44%). In 42% of the borderline tumors and carcinomas only one marker was demonstrated, in 7% none. Here, immunohistochemistry may indicate the most adequate marker. Tumor marker expression was markedly heterogenous: tumor areas with strong, weak, and no reaction were adjacent. The tumor markers revealed no specificity for malignancy or disease.     

Immunohistochemical distribution of tumor-associated antigen CA6 in gynecological neoplasms as detected by monoclonal antibody DS6.

DS6 is a murine monoclonal antibody developed using ovarian papillary serous adenocarcinoma as the immunogen. DS6 immunohistochemically reacts with a tumor-associated antigen, CA6, which has a limited range of expression in normal human tissues and is not expressed by benign mesothelium. We have studied the spectrum of immunohistochemical reactivity of antibody DS6 in 293 formalin-fixed, paraffin-embedded human gynecological neoplasms. The CA6 antigen shows strong expression in serous adenocarcinomas of the ovary (56/58 cases) and endometrium (6/6). CA6 is also expressed by the majority of ovarian endometrioid adenocarcinomas and Brenner tumors and by the majority of endometrioid adenocarcinomas, mucinous adenocarcinomas, and clear cell adenocarcinomas of the endometrium. CA6 is detected in 14% of ovarian clear cell carcinomas and is not detected in ovarian mucinous cystadenomas (0/7), mucinous intestinal-type borderline tumors (0/8), mucinous adenocarcinomas (0/10), or in malignant mesotheliomas (0/8). In neoplasms with papillary or glandular growth patterns, CA6 is detected along luminal cell membranes. CA6 is also seen along peripheral cell membranes and focally in the cytoplasm in some epithelial neoplasms. There is heterogeneity in immunohistochemical staining for DS6 both within an individual neoplasm and between neoplasms. Reactivity is not detected in neoplasms of sex cord-stromal, mesenchymal or germ cell origin.     

Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors

OBJECTIVES: The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. METHODS: For patient identification a database was used, in which data from all patients treated for gynecologic malignancies in the Department of Gynecologic Oncology, University Hospital Groningen, The Netherlands, are compiled. Between 1982 and 1997, 44 patients with borderline ovarian tumors were identified. Clinical data and serum CA-125 and CEA levels were retrieved from the database. CA 19-9 levels were determined in retrospect in available stored preoperative (24 patients) and follow-up (43 patients) serum samples. RESULTS: Preoperative CA 125 levels were elevated in 8 of 33 (24%), CEA levels in 3 of 32 (9%), and CA 19-9 levels in 11 of 24 (46%) cases. In patients with mucinous tumors preoperative CA 19-9 was more frequently elevated (8/14, 57%) than CA 125 (3/20, 15%) (P = 0.02) or CEA (2/18, 11%) (P = 0.02). Complete follow-up serum CA 125, CEA, and CA 19-9 levels were available for 43 of 44 patients. Median follow-up was 84 months (range, 22-204). During follow-up two patients (5%) had recurrent disease. In one patient CA 125 became elevated at the time of recurrence; in the other patient (in retrospect) the CA 19-9 level did not return to normal after surgery, but kept rising, preceding clinical symptoms of recurrence for 13 months. CONCLUSIONS: If one chooses to use serum markers in follow-up of mucinous borderline ovarian tumors CA 19-9 should be included. Measurement of serum tumor markers in the follow-up of patients with borderline ovarian tumors may lead to earlier detection of recurrence in only a very small proportion of patients, while the clinical value of earlier detection of recurrence remains to be established.     

Prognostic value of elevated preoperative serum CA125 in ovarian tumors of low malignant potential: a multinational collaborative study (ANZGOG0801)

Objective

Previous studies on prognostic factors in ovarian tumors of low malignant potential (LMP) were too small for robust conclusions. We examined the prognostic impact of preoperative serum CA125 ≥ 50 U/ml levels in patients diagnosed with ovarian LMP tumors in a large multinational cohort.

Methods

This retrospective study included 940 patients with ovarian LMP tumors diagnosed between 1985 and 2008 at six gynecologic cancer centers. Patients either had radical treatment (bilateral salpingo-oophorectomy with or without hysterectomy) or conservative, fertility-sparing treatment. Multivariate Cox proportional hazard models were used to determine independent prognostic factors for disease-free (DFS) and overall survival (OS). Based on receiver operating characteristic curve (ROC), a preoperative serum CA125 level ≥ 50 U/ml was considered “elevated”.

Results

CA125 was more often elevated in serous than in mucinous tumors and in advanced FIGO stages (2 to 4) compared to stage1. DFS at 5 years was 89% and 95% in patients with elevated and normal CA125 levels (p < 0.05). Similarly, the 5-year OS was 90% among patients with elevated CA125 compared to 95% among patients with normal levels (p < 0.05). For both DFS and OS elevated CA125 levels and advanced stages of the disease were independent prognostic factors. Analysis of subgroups revealed that CA125 was only prognostic in serous LMP tumors.

Conclusions

In the context of serous ovarian LMP tumors, elevated preoperative serum CA125 represents a biomarker independently associated with impaired disease-free and overall survival. CA125 is available in most centers and could inform surgeons about the risk of treatment failure.