J.G. Aalders

Explanation of the limited correlation between tumor CA 125 content and serum CA 125 antigen levels in patients with ovarian tumors

The concentration of the tumor marker CA 125 in tumor tissue, cyst fluid, ascites fluid, and serum from patients with epithelial ovarian tumors was quantitated. Immunohistologic studies showed that CA 125 was present in 90% of the nonmucinous epithelial ovarian tumors. Quantitative analysis of the fluid from 57 cysts revealed that CA 125 was present in concentrations of up to 2140,000 U/ml in samples from malignant nonmucinous epithelial ovarian lesions, and up to 116,000 U/ml in mucinous tumors, but also in concentrations of up to 371,000 U/ml in benign serous cystadenomas. In contrast, pre‐operative serum CA 125 levels were elevated in almost all of the patients with malignant ovarian tumors but not in most of those with benign ovarian tumors. These findings suggest that in benign ovarian tumors there is an effective barrier between the cyst fluid and the circulation that prevents the appearance of CA 125 in the serum, whereas in malignant tumors infiltrative growth leads to the release of antigen into the circulation. Furthermore, CA 125 values in ascites fluids were up to 130 times higher than the serum antigen levels, which indicates that the peritoneum serves as a barrier for high molecular weight tumor antigens. The current results show that tumor basement membranes and peritoneal barriers play a notable role in the transit of tumor antigens, one which must be taken into account in the monitoring of serum marker levels of cancer patients.

The tumor marker CA 125 is a common constituent of normal cervical mucus

The presence of the tumor marker CA 125 was studied in the cervices of healthy women. Immunohistochemical staining of normal cervical tissue demonstrated the presence of CA 125 in the tall columnar cells of the endocervical epithelium but not in the ectocervical squamous epithelium. We measured very high levels of CA 125 in liquefied cervical mucus from women with regular menstrual cycles. At midcycle, levels ranged from 14,200 to 153,000 U/ml (n = 13) in cervical mucus, while normal levels less than 35 U/ml were found in the corresponding serum samples. Levels of CA 125 in cervical mucus are comparable to the high levels found in cyst fluids from ovarian tumors (median 24,600 U/ml, n = 25). When secretion of cervical mucus was stimulated by ethinyl estradiol, equally high levels were found (7900 to 138,000 U/ml, n = 10). We conclude that the tumor marker CA 125 is synthesized and secreted by normal endocervical cells. Apparently an effective barrier exists between the endocervical mucosa and the circulation.

Significance of serum SCC antigen as a tumor marker in patients with squamous cell carcinoma of the vulva

The significance of serum SCC antigen as a tumor marker was investigated in 94 women with squamous cell carcinoma of the vulva. The incidence of elevated serum SCC levels varied from 10% in FIGO stage I to 40% in FIGO stage IV. We did not observe a correlation between elevated pretreatment SCC values and the presence of lymph node metastases. During follow-up, elevated serum SCC values were observed in 8 of 19 patients (42%) with recurrent or progressive disease. It is concluded that the determination of serum SCC levels does not provide additional information in the staging of squamous cell vulvar carcinoma, but can be useful for the early detection of recurrent disease during follow-up in some patients. However, elevated serum SCC levels were also found in 25% of patients without demonstrable tumor activity during follow-up and benign skin disorders were recognized as a cause of false-positive SCC results.

Risk factors in gestational trophoblastic disease, and consequences for primary treatment

Treatment with methotrexate (MTX) for two patients with gestational choriocarcinoma proved to be inadequate; subsequently both patients received a combination of cis-platinum, cyclophosphamide, actinomycin D and etoposide. These histories demonstrate the need for better prediction of the efficacy of MTX treatment. Baghshawe and Goldstein developed scoring systems to recognize patients requiring primary combination chemotherapy. The Dutch Working Group for Trophoblastic Tumors recently introduced a simplified scoring system to classify these patients. In order to compare these three scoring systems to predict the effect of primary treatment with MTX a retrospective study was made of 37 patients. MTX treatment failures were predictable in 8 out of 13 patients using Bagshawes system and 6 out of 13 by the Dutch scoring system. The specificity was 88 and 92%, respectively. Goldsteins scoring system proved to be the least sensitive, but very specific.

Levels of CA 125 in patients with recurrent carcinoma of the fallopian tube: two case histories.

Our study reports 6 patients with advanced adenocarcinoma of the fallopian tube, with elevated levels of serum CA 125 (greater than 35 U/ml). In two patients the serum CA 125 values were followed during treatment. In one of them the CA 125 values decreased during clinical remission and increased at the time of tumor progression. In the second patient we observed increasing levels of CA 125 preceding clinical evidence of recurrent disease. The possible usefulness of CA 125 for monitoring patients with tubal cancer is discussed.

Circulating antibodies against human chorionic gonadotropin following trophoblastic disease

The presence of antibodies against human chorionic gonadotropin (hCG) is described in a patient who was treated for persistent trophoblastic disease. These antibodies remained detectable over a 14-month period of observation. In 15 other patients, successfully treated for trophoblastic disease, their presence could not be demonstrated. The binding affinity for labeled hCG was investigated by polyethylene glycol precipitation, by complex formation with protein A-Sepharose, and by gel filtration. Circulating antibodies against hCG may interfere with immunological serum hCG estimations.

CA 125 in tumor tissues, cyst fluids, cervical mucus and serum

Ce l l u l a r p r o l i f e r a t i o n i s potent ly st imulated by a fami ly of hormonally act ive polypept ides, the growth fac tors . Growth f_actors have the po ten t ia l to induce c e l l u l a r t ranstormat ion i f they act at the wrong time or in the wrong place. Factors inducing c e l l t ransformat ion have been shown to be a r e l a t i v e to epidermal growth fac to r (EGF) and in te rac t with c e l l u ] a r receptors .f_or EGF (EGF Like f ac to r s ) , lhe aim o• t h i s study was to inves t iga te ovarian carcinomas f o r the presence o• EGF l i k e fac to rs (EGF-F) in co r re la t i on to c l i n i c a l parameters. Specimens of ovarian carcinomas and nonmalignant t i ssues were ext rac ted with 1 M acet ic acid, centri• end the supernmten ts analyzed • the presence o• EGF F by a EGF radio receptorassay, lhe ~actor content i s expressed as EGF competing a c t i v i t y in n~ EGF units/mg pro te in . In ex t rac ts of nonmalignant t i ssues, i . e . normal ovar ies and myometrJum, and ovarian carcinomas EGF-F could be detected. However, the fac to r contents o f the d i f f e r e n t ex t rac ts var ied w ide l y . . I n nonmalignant t issues fac to r leve ls did not exceed 6 ng EGF units/mg. 18/42 ovarian carcinomas contained high fac to r concentrat ion between 6-17 EGF units/mg. Pat ients were separated in two groups with low (<6 ng) and high (>6 n~) EGF-F t i ssue leve ls . Both groups were cor re la ted with c l i n i c a l date. No d i f fe rences were noticed to h i s t o l o g i c a l subtype and steroidhormonereceptorstatus. Low res idua l tumorrest (< 2 cm) a f t e r primary surgery was found in 11/20 cases with low • content compared to 4/15 cases with high • content. The responserate to a c is-p lat inum combinat ion chemotherapy in the group with low fac to r concent r a t i o n was: 4/21 progressive disease (PD) 3/21 no change (n.c. ) and 14/21 remission (CR+PR). The resu l t s in the group with high fac to r concentrat ion were: 9/24 PD, 5/14 n.c. and 0/14 CR+PR. Dit• in the su rv i va l t ime of both groups were also not iced. However, the case number is too low f o r de ta i led s t a t i s t i c a l analysis, lhese results let assume that the bioIooicaI be havieur of ovarian carcinomas couId be influenced by its content of EGF like grovrch factors.

CA 125: A useful marker in endometrial carcinoma

In a retrospective study 121 patients with endometrial cancer were examined. In addition, 20 primary endometrial adenocarcinomas were tested immunohistochemically for CA 125. All tumor tissues were demonstrated to contain CA 125. However, only 25% of 110 patients had elevated CA 125 levels in serum before treatment. The incidence of elevated CA 125 serum levels increased with higher tumor staging up to 55% and 86% in surgical Stages III and IV, respectively. In Stage I and II disease (International Federation of Gynecology and Obstetrics) elevated serum levels before treatment correlated with the presence of tumor tissues outside the uterine body or outside the uterus, respectively, as was determined histopathologically after operation. In addition a close correlation between elevated levels and vessel invasion of tumor cells was revealed. Serum levels of CA 125 paralleled the clinical course of disease. Tumor recurrence in the abdomen can be preceded by an increase of serum CA 125 levels.