CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and fallopian tube. I. Immunohistochemical detection.

The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Müllerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true "tumour marker", but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation.

CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and Fallopian tube. II. Immunoradiometric determination in secretions, tissue extracts and serum.

The study deals with the occurrence of cancer antigen 125 (CA 125) in the normal and neoplastic uterine cervix, endometrium and fallopian tube and its applicability as a tumour marker. CA 125 concentrations were measured in 52 secretion specimens, in cytosol fractions of 97 tissue biopsies and in serum from 47 women with nonmalignant disorders and from 334 patients with carcinomas. High quantities of CA 125 (780-454860 U/ml) were detected in cervical mucus, intra-uterine and tubal fluid, exceeding those in the corresponding serum samples by factors of up to 2000. CA 125 concentrations were 9-53 fold higher in cytosol fractions of normal and neoplastic glandular epithelia of the endocervix and endometrium than in those of cervical squamous epithelia and the cervical wall. Despite similarly high antigen concentrations in normal glandular epithelia and adenocarcinomas serum levels elevated to above 65 U/ml were only found in patients with malignant tumours. The positivity rates in serum increased with tumour extent and were 0-43% for primary and 63-79% for recurrent cervical, endometrial and tubal adenocarcinomas. During long-term follow-up, CA 125 serum concentrations were concordant with the clinical course in 10 out of 11 patients with progressive carcinomas. According to these results, the release of CA 125 into the peripheral blood is apparently dependent on the infiltrative growth and the mass of the tumour rather than on the local tissue concentrations. The clinical use of CA 125 is limited to the detection of advanced adenocarcinomas of the Müllerian duct.

Expression of IgA and secretory component in the normal and in adenocarcinomas of Fallopian tube, endometrium and endocervix.

The occurrence and localization of IgA and secretory components (SC) were examined in the normal and in adenocarcinomas of Fallopian tube, endometrium and endocervix. IgA-containing immunocytes were identified in the stroma of 90% of normal Fallopian tubes. It is suggested that the Fallopian tube may have an immunological function and may, together with the endocervix, constitute the local secretory immune system of the female genital tract. IgA and SC were frequently demonstrated in the cytoplasm and luminal secretion of adenocarcinomas of the endocervix, endometrium and Fallopian tube. This study has shown a decrease in immunoreactivity of SC among poorly differentiated adenocarcinomas but has failed to demonstrate any correlation between the expression of IgA and the degree of differentiation of the tumours. Secretory component appears, therefore, to be more useful than IgA as an indicator of secretory activity and differentiation of adenocarcinomas of the female genital tract.

[Estrogen and progesterone receptors in malignant ovarian neoplasms]. / Ostrogen- und Progesteronrezeptoren in malignen ovarialtumoren.

Estrogen receptors (ER) and progesterone receptors (PR) were evaluated in 173 primary ovarian cancers and in 6 ovarian metastases. In epithelial ovarian carcinomas 63% had ER and 46% PR. Almost all granulosa cell tumours were receptor-positive, while sarcomas, dysgerminomas, and teratomas lacked ER and PR. Both receptors were found less often in tumours of the histological grade I than in those of grade II and III. During the development of metastases and during chemotherapy there was a loss of PR in 27% and 53% of the cases, respectively, while the amount of ER remained more or less constant. In addition to ovarian cancers ER and PR were present in carcinomas of the fallopian tube as well. ER-negative and especially PR-negative tumours seemed to respond better to chemotherapy than receptor-positive carcinomas. The possible significance of ER and PR with regard to the success of an endocrine treatment is discussed.